Skin surface cooling improves orthostatic tolerance following prolonged head-down bed rest

PubMed Central

Keller, David M.; Low, David A.; Davis, Scott L.; Hastings, Jeff

2011-01-01

Prolonged exposure to microgravity, as well as its ground-based analog, head-down bed rest (HDBR), reduces orthostatic tolerance in humans. While skin surface cooling improves orthostatic tolerance, it remains unknown whether this could be an effective countermeasure to preserve orthostatic tolerance following HDBR. We therefore tested the hypothesis that skin surface cooling improves orthostatic tolerance after prolonged HDBR. Eight subjects (six men and two women) participated in the investigation. Orthostatic tolerance was determined using a progressive lower-body negative pressure (LBNP) tolerance test before HDBR during normothermic conditions and on day 16 or day 18 of 6° HDBR during normothermic and skin surface cooling conditions (randomized order post-HDBR). The thermal conditions were achieved by perfusing water (normothermia ∼34°C and skin surface cooling ∼12–15°C) through a tube-lined suit worn by each subject. Tolerance tests were performed after ∼30 min of the respective thermal stimulus. A cumulative stress index (CSI; mmHg LBNP·min) was determined for each LBNP protocol by summing the product of the applied negative pressure and the duration of LBNP at each stage. HDBR reduced normothermic orthostatic tolerance as indexed by a reduction in the CSI from 1,037 ± 96 mmHg·min to 574 ± 63 mmHg·min (P < 0.05). After HDBR, skin surface cooling increased orthostatic tolerance (797 ± 77 mmHg·min) compared with normothermia (P < 0.05). While the reduction in orthostatic tolerance following prolonged HDBR was not completely reversed by acute skin surface cooling, the identified improvements may serve as an important and effective countermeasure for individuals exposed to microgravity, as well as immobilized and bed-stricken individuals. PMID:21454746

Improving glucose tolerance by reducing weight gain in a polygenic obese mouse model: use of a high protein diet.

PubMed

Blair, A R; Strube, M L; Proietto, J; Andrikopoulos, S

2015-03-01

Diets to decrease body weight have limited success in achieving and importantly maintaining this weight loss long-term. It has recently been suggested that energy intake can be regulated by the amount of protein ingested, termed the protein leverage hypothesis. In this study, we determined whether a high protein diet would be effective in achieving and maintaining weight loss in a genetically obese model, the New Zealand Obese (NZO) mouse. NZO and C57BL/6J (C57) control mice were fed a high protein or chow diet for 5 weeks from weaning (3 weeks of age). Body weight and food intake were determined. Mice on the same diet were bred to produce offspring that were fed either a chow or high protein diet. Body weight, food intake, and glucose tolerance were determined. Feeding NZO and C57 mice a high protein diet for 5 weeks resulted in reduced food intake and consequently energy intake and body weight gain compared with mice on a chow diet. NZO mice fed a high protein diet showed a significant improvement in glucose tolerance compared with their chow-fed counterparts, while no difference was seen in C57 mice fed chow or protein diet. The offspring of NZO mice that were fed a high protein diet during gestation and weaning were also lighter and displayed improved glucose tolerance compared with chow fed animals. We conclude that a high protein diet is a reasonable strategy to reduce body weight gain and improve glucose tolerance in the NZO mouse, a polygenic model of obesity. © Georg Thieme Verlag KG Stuttgart · New York.

MicroRNA156 improves drought stress tolerance in alfalfa (Medicago sativa) by silencing SPL13.

PubMed

Arshad, Muhammad; Feyissa, Biruk A; Amyot, Lisa; Aung, Banyar; Hannoufa, Abdelali

2017-05-01

Alfalfa (Medicago sativa) is an important forage crop that is often grown in areas that frequently experience drought and water shortage. MicroRNA156 (miR156) is an emerging tool for improving various traits in plants. We tested the role of miR156d in drought response of alfalfa, and observed a significant improvement in drought tolerance of miR156 overexpression (miR156OE) alfalfa genotypes compared to the wild type control (WT). In addition to higher survival and reduced water loss, miR156OE genotypes also maintained higher stomatal conductance compared to WT during drought stress. Furthermore, we observed an enhanced accumulation of compatible solute (proline) and increased levels of abscisic acid (ABA) and antioxidants in miR156OE genotypes. Similarly, alfalfa plants with reduced expression of miR156-targeted SPL13 showed reduced water loss and enhanced stomatal conductance, chlorophyll content and photosynthetic assimilation. Several genes known to be involved in drought tolerance were differentially expressed in leaf and root of miR156 overexpression plants. Taken together, our findings reveal that miR156 improves drought tolerance in alfalfa at least partially by silencing SPL13. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Physiological and molecular characterization of drought responses and identification of candidate tolerance genes in cassava

PubMed Central

Turyagyenda, Laban F.; Kizito, Elizabeth B.; Ferguson, Morag; Baguma, Yona; Agaba, Morris; Harvey, Jagger J. W.; Osiru, David S. O.

2013-01-01

Cassava is an important root crop to resource-poor farmers in marginal areas, where its production faces drought stress constraints. Given the difficulties associated with cassava breeding, a molecular understanding of drought tolerance in cassava will help in the identification of markers for use in marker-assisted selection and genes for transgenic improvement of drought tolerance. This study was carried out to identify candidate drought-tolerance genes and expression-based markers of drought stress in cassava. One drought-tolerant (improved variety) and one drought-susceptible (farmer-preferred) cassava landrace were grown in the glasshouse under well-watered and water-stressed conditions. Their morphological, physiological and molecular responses to drought were characterized. Morphological and physiological measurements indicate that the tolerance of the improved variety is based on drought avoidance, through reduction of water loss via partial stomatal closure. Ten genes that have previously been biologically validated as conferring or being associated with drought tolerance in other plant species were confirmed as being drought responsive in cassava. Four genes (MeALDH, MeZFP, MeMSD and MeRD28) were identified as candidate cassava drought-tolerance genes, as they were exclusively up-regulated in the drought-tolerant genotype to comparable levels known to confer drought tolerance in other species. Based on these genes, we hypothesize that the basis of the tolerance at the cellular level is probably through mitigation of the oxidative burst and osmotic adjustment. This study provides an initial characterization of the molecular response of cassava to drought stress resembling field conditions. The drought-responsive genes can now be used as expression-based markers of drought stress tolerance in cassava, and the candidate tolerance genes tested in the context of breeding (as possible quantitative trait loci) and engineering drought tolerance in transgenics. PMID:23519782

How do yeast cells become tolerant to high ethanol concentrations?

PubMed

Snoek, Tim; Verstrepen, Kevin J; Voordeckers, Karin

2016-08-01

The brewer's yeast Saccharomyces cerevisiae displays a much higher ethanol tolerance compared to most other organisms, and it is therefore commonly used for the industrial production of bioethanol and alcoholic beverages. However, the genetic determinants underlying this yeast's exceptional ethanol tolerance have proven difficult to elucidate. In this perspective, we discuss how different types of experiments have contributed to our understanding of the toxic effects of ethanol and the mechanisms and complex genetics underlying ethanol tolerance. In a second part, we summarize the different routes and challenges involved in obtaining superior industrial yeasts with improved ethanol tolerance.

Enhanced salt tolerance of alfalfa (Medicago sativa) by rstB gene transformation.

PubMed

Zhang, Wan-Jun; Wang, Tao

2015-05-01

Generating salt tolerance forage plant is essential for use of the land affected by high salinity. A salt tolerance gene rstB was used as a selectable marker gene in Agrobacterium-mediated transformation of tobacco under a selective regime of 170mM NaCl. The transgenic plants showed clear improvement in salt tolerance. To improve salt tolerance of alfalfa (Medicago sativa L.), rstB gene was introduced into alfalfa genome by Agrobacterium-mediated transformation. No abnormal phenotype was observed among the transgenic plants when compared with wild type (wt) plants. Significant enhancement of resistance to salt-shock treatment was noted on the rstB transgenic (T0) plants. Transgenic second-generation (T1) seeds showed improved germination rate and seedling growth under salt-stress condition. Hindered Na(+) accumulation, but enhanced Ca(2+) accumulation was observed on the rstB T1 plants when subjected to salt-stresses. Enhanced calcium accumulation in transgenic plants was also verified by cytohistochemical localization of calcium. Under salt-stress of 50mM NaCl, about 15% of the transgenic plants finished their life-cycle but the wt plants had no flower formation. The results demonstrated that the expression of rstB gene improved salt tolerance in transgenic alfalfa. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

[Repeated body position change training can improve human head-down tilt tolerance].

PubMed

Wu, Bin; Wu, Ping; Xue, Yue-Ying; Liu, Xing-Hua; Wang, Yan-Lei; Jiang, Shi-Zhong

2008-02-01

To verify the hypothesis that repeated body position change training can improve human head-down tilt (HDT) tolerance. Six young healthy subjects were trained with repeated position change for 9 times and 11 days according to protocol of alternative head-down and head-up tilts, each time of training lasted for about 35 min. Their HDT tolerance (- 30 degrees/30 min) were determined before and after training. (1) Compared with the data before training, subjects' symptom scores during HDT test after training decreased significantly (6.00 +/- 3.79 vs 1.00 +/- 0.63, P < 0.05), magnitude of the decreased heart rate increased significantly (-0.6 +/- 2.5 vs -4.4 +/- 3.6, P < 0.01). (2) Before training, blood flow volume of internal jugular vein (IJV) during HDT decreased significantly and that of internal carotid artery (ICA) increased significantly at the beginning period of HDT compared with pre-HDT (P < 0.01), while blood flow volume of the common carotid artery (CCA) presented increasing trend. After training, there was no significant difference in blood flow volume of IJV between during HDT and pre-HDT, that of ICA and CCA presented decreasing trend in the final period of HDT compared with Pre-HDT. Repeated body position change training can improve human head-down tilt tolerance. And its main causation is that headward shift of blood volume is restrained to some extend during HDT after training.

Changes in glucose-elicited blood metabolite responses following weight loss and long term weight maintenance in obese individuals with impaired glucose tolerance.

PubMed

Geidenstam, Nina; Danielsson, Anders P H; Spégel, Peter; Ridderstråle, Martin

2016-03-01

Weight loss improves insulin sensitivity and glucose tolerance in obese subjects with impaired glucose tolerance (IGT), but the long term dynamic effects on blood metabolites other than glucose during an oral glucose tolerance test (OGTT), are largely unknown. Here, we studied changes in OGTT-elicited metabolite patterns in obese subjects during a diet-induced weight loss study. Blood samples from 14 obese individuals with IGT were collected at 0, 30 and 120 min during a standard 75 g OGTT at baseline (BMI 44 ± 2 kg/m(2)), after weight loss (BMI 36 ± 2 kg/m(2)) and after weight maintenance (BMI 35 ± 2 kg/m(2)). Serum metabolite levels were analyzed by gas chromatography/mass spectrometry and compared to a lean glucose tolerant group. Changes in the OGTT-elicited metabolite patterns occurred differentially during weight loss and weight maintenance. Enhanced suppression of aromatic amino acids were associated with decreased insulinogenic index observed after weight loss (tyrosine: r=0.72, p=0.013; phenylalanine: r=0.63, p=0.039). The OGTT-elicited suppression and/or lack of increase in levels of glutamate, glutamine, isoleucine, leucine, and the fatty acids laurate, oleate and palmitate, improved towards the lean profile after weight maintenance, paralleling an improvement in glucose tolerance. The greater heterogeneity in the response before and after weight loss in the obese, compared to lean subjects, was markedly reduced after weight maintenance. Diet-induced weight loss followed by weight maintenance results in changes in metabolite profiles associated with either hepatic insulin sensitivity or peripheral glucose tolerance. Our results highlight the importance of evaluating the effects of weight loss and weight maintenance separately. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Advanced cloud fault tolerance system

NASA Astrophysics Data System (ADS)

Sumangali, K.; Benny, Niketa

2017-11-01

Cloud computing has become a prevalent on-demand service on the internet to store, manage and process data. A pitfall that accompanies cloud computing is the failures that can be encountered in the cloud. To overcome these failures, we require a fault tolerance mechanism to abstract faults from users. We have proposed a fault tolerant architecture, which is a combination of proactive and reactive fault tolerance. This architecture essentially increases the reliability and the availability of the cloud. In the future, we would like to compare evaluations of our proposed architecture with existing architectures and further improve it.

Contamination avoidance devices for poppettype shutoff valves

NASA Technical Reports Server (NTRS)

Endicott, D. L.

1973-01-01

The determination of the cycle life is reported of the scal closure of a typical poppet-type shutoff valve in an uncontaminated GH2 environment and then compared this component performance with simulated operation with GN2 and LN2 containing controlled amounts of AL2O3 contaminant particles. The original valve design was tested for contamination damage tolerance characteristics under full-flow and cyclic-operating conditions, redesigned to improve the damage tolerance to contaminants, and then retested. The redesigned valve was found to have acceptable tolerance characteristics under all full-flow conditions and cyclic operation with small (25-75 microns) particulate contamination. The tolerance characteristics of the valve under cyclic conditions with large (75-250 microns) particulate contamination was improved but was not found to be completely satisfactory.

Comparison of intradialytic hemodynamic tolerance between on-line hemodiafiltration and acetate-free biofiltration with profiled potassium dialysate concentration.

PubMed

Kosmadakis, George; Correia, Enrique Da Costa; Somda, Frederic; Aguilera, Didier

2017-01-01

Intradialytic hypotensive episodes are deleterious for hemodialysis (HD) patients. Acetate-free biofiltration with profiled potassium (AFBK) dialysate concentration may improve their cardiovascular stability. The aim of the present crossover study was to compare intradialytic hemodynamic tolerance and biological parameters between online hemodiafiltration (olHDF) and AFBK. Ten frail HD patients (8 males) with a mean age of 66.71- ± 12.31 years were studied for three months on olHDF and AFBK. There was a significant reduction of the hypotensive episodes during the AFBK period compared to the olHDF period. Mean intradialytic systolic and diastolic blood pressures were significantly higher during the AFBK period. There was a significant postdialytic increase in serum sodium concentration with the AFBK compared to olHDF. The dry weight and ultrafiltration indices were significantly higher, and the Kt/V was significantly lower during the AFBK period. Serum albumin concentration significantly increased during the AFBK period. AFBK leads to a significantly improved intradialytic tolerance in hemodynamically instable HD patients.

Molecular breeding in Brassica for salt tolerance: importance of microsatellite (SSR) markers for molecular breeding in Brassica.

PubMed

Kumar, Manu; Choi, Ju-Young; Kumari, Nisha; Pareek, Ashwani; Kim, Seong-Ryong

2015-01-01

Salinity is one of the important abiotic factors for any crop management in irrigated as well as rainfed areas, which leads to poor harvests. This yield reduction in salt affected soils can be overcome by improving salt tolerance in crops or by soil reclamation. Salty soils can be reclaimed by leaching the salt or by cultivation of salt tolerance crops. Salt tolerance is a quantitative trait controlled by several genes. Poor knowledge about mechanism of its inheritance makes slow progress in its introgression into target crops. Brassica is known to be a good reclamation crop. Inter and intra specific variation within Brassica species shows potential of molecular breeding to raise salinity tolerant genotypes. Among the various molecular markers, SSR markers are getting high attention, since they are randomly sparsed, highly variable and show co-dominant inheritance. Furthermore, as sequencing techniques are improving and softwares to find SSR markers are being developed, SSR markers technology is also evolving rapidly. Comparative SSR marker studies targeting Arabidopsis thaliana and Brassica species which lie in the same family will further aid in studying the salt tolerance related QTLs and subsequent identification of the "candidate genes" and finding out the origin of important QTLs. Although, there are a few reports on molecular breeding for improving salt tolerance using molecular markers in Brassica species, usage of SSR markers has a big potential to improve salt tolerance in Brassica crops. In order to obtain best harvests, role of SSR marker driven breeding approaches play important role and it has been discussed in this review especially for the introgression of salt tolerance traits in crops.

Molecular breeding in Brassica for salt tolerance: importance of microsatellite (SSR) markers for molecular breeding in Brassica

PubMed Central

Kumar, Manu; Choi, Ju-Young; Kumari, Nisha; Pareek, Ashwani; Kim, Seong-Ryong

2015-01-01

Salinity is one of the important abiotic factors for any crop management in irrigated as well as rainfed areas, which leads to poor harvests. This yield reduction in salt affected soils can be overcome by improving salt tolerance in crops or by soil reclamation. Salty soils can be reclaimed by leaching the salt or by cultivation of salt tolerance crops. Salt tolerance is a quantitative trait controlled by several genes. Poor knowledge about mechanism of its inheritance makes slow progress in its introgression into target crops. Brassica is known to be a good reclamation crop. Inter and intra specific variation within Brassica species shows potential of molecular breeding to raise salinity tolerant genotypes. Among the various molecular markers, SSR markers are getting high attention, since they are randomly sparsed, highly variable and show co-dominant inheritance. Furthermore, as sequencing techniques are improving and softwares to find SSR markers are being developed, SSR markers technology is also evolving rapidly. Comparative SSR marker studies targeting Arabidopsis thaliana and Brassica species which lie in the same family will further aid in studying the salt tolerance related QTLs and subsequent identification of the “candidate genes” and finding out the origin of important QTLs. Although, there are a few reports on molecular breeding for improving salt tolerance using molecular markers in Brassica species, usage of SSR markers has a big potential to improve salt tolerance in Brassica crops. In order to obtain best harvests, role of SSR marker driven breeding approaches play important role and it has been discussed in this review especially for the introgression of salt tolerance traits in crops. PMID:26388887

Effects of a NTG-based chemical mutagenesis on the propamocarb-tolerance of the nematophagous fungus Lecanicillium attenuatum.

PubMed

Xie, Ming; Li, Qian; Hu, Xin-Ping; Zhang, Yan-Jun; Peng, De-Liang; Zhang, Xiao-Lin

2017-09-01

Lecanicillium attenuatum is an important nematophagous fungus with potential as a biopesticide for control of plant-pathogenic nematodes. However, relatively low fungicide-tolerance limits its application in the field. To improve the propamocarb-tolerance of L. attenuatum, a NTG-based mutagenesis system was established. Among different combinations of NTG concentration and treatment time in the first-round NTG treatment, the treatment of 1.0mg/ml NTG for 60min gave a proper conidial lethality rate of 84.6% and the highest positive mutation rate of 7.7%, and then produced the highest propamocarb-tolerant mutant LA-C-R1-T4-M whose EC 50 value reached to 1050.0μg/ml. The positive mutation range was 105.1% in the first-round NTG treatment. Multiple-round NTG treatment was further employed to enhance the propamocarb tolerance of L. attenuatum. The positive mutation range was significantly accumulated to 179.3% on the third-round NTG treatment, and then appeared to level-off and remained constant. These results indicated that multiple-round NTG treatment had a significant accumulative effect on fungal tolerance to propamocarb. Among all chemical-mutants, the LA-C-R3-M was the highest tolerant to propamocarb, whose EC 50 value was increased 2.79-fold compared to the wild-type strain, and it was mitotic stable after 20 passages on PDA medium. Colony growth, conidia yield and conidial germination on plates, and parasitism of nematode eggs of M. incognita and H. glycines were not significantly changed by the NTG-based mutagenesis compared to the wild-type strain in either single- or multiple-round NTG treatment. In conclusion, we succeeded in improving the propamocarb tolerance of L. attenuatum via the optimized NTG-based mutagenesis system. The improved strain LA-C-R3-M could be potentially applied with propamocarb in the field. Copyright © 2016 Elsevier B.V. All rights reserved.

Stress inducible overexpression of AtHDG11 leads to improved drought and salt stress tolerance in peanut (Arachis hypogaea L.)

NASA Astrophysics Data System (ADS)

Banavath, Jayanna N.; Chakradhar, Thammineni; Pandit, Varakumar; Konduru, Sravani; Guduru, Krishna K.; Akila, Chandra S.; Podha, Sudhakar; Puli, Chandra O. R.

2018-03-01

Peanut is an important oilseed and food legume cultivated as a rain-fed crop in semi-arid tropics. Drought and high salinity are the major abiotic stresses limiting the peanut productivity in this region. Development of drought and salt tolerant peanut varieties with improved yield potential using biotechnological approach is highly desirable to improve the peanut productivity in marginal geographies. As abiotic stress tolerance and yield represent complex traits, engineering of regulatory genes to produce abiotic stress-resilient transgenic crops appears to be a viable approach. In the present study, we developed transgenic peanut plants expressing an Arabidopsis homeodomain-leucine zipper transcription factor (AtHDG11) under stress inducible rd29Apromoter. A stress-inducible expression of AtHDG11 in three independent homozygous transgenic peanut lines resulted in improved drought and salt tolerance through up-regulation of known stress responsive genes(LEA, HSP70, Cu/Zn SOD, APX, P5CS, NCED1, RRS5, ERF1, NAC4, MIPS, Aquaporin, TIP, ELIP ) in the stress gene network , antioxidative enzymes, free proline along with improved water use efficiency traits such as longer root system, reduced stomatal density, higher chlorophyll content, increased specific leaf area, improved photosynthetic rates and increased intrinsic instantaneous WUE. Transgenic peanut plants displayed high yield compared to non-transgenic plants under both drought and salt stress conditions. Holistically, our study demonstrates the potentiality of stress-induced expression of AtHDG11 to improve the drought, salt tolerance in peanut.

Efficacy, safety, tolerability and price of newly approved drugs in solid tumors.

PubMed

Barnes, Tristan A; Amir, Eitan; Templeton, Arnoud J; Gomez-Garcia, Susana; Navarro, Beatriz; Seruga, Bostjan; Ocana, Alberto

2017-05-01

New anti-cancer drugs utilize diverse mechanisms of action. Here we evaluate their differential efficacy, safety, tolerability and price. Drugs approved for solid tumor treatment between 2000 and 2015 were identified and analyzed in subgroups: agents targeting oncogenes (group 1), anti-angiogenics (group 2), immunotherapy (group 3), and chemotherapy (group 4). Hazard ratios (HRs) were extracted from the registration trials and pooled in a meta-analysis. Odds ratios for toxic death, treatment discontinuation and grade 3-4 toxicity were compared to control groups. The Micromedex Red Book was used to calculate the monthly price. Analysis included 74 studies comprising 48,527 patients. Progression-free survival (PFS) was improved to a greater degree with groups 1 and 2 than with groups 3 and 4, (pooled HR: 0.54, 0.56, 0.63, and 0.76 for groups 1-4 respectively, p for difference <0.001). Compared to PFS, there was a lower magnitude of improvement overall survival in all groups and the degree of benefit was less for group 4 than for other groups (pooled HR: 0.77, 0.78, 0.68, and 0.83 for groups 1-4 respectively, p for difference=0.007). Compared to control groups in individual trials, immunotherapy was associated with better safety and tolerability than other groups. Drug prices have increased over time with no significant difference between groups. There was no meaningful correlation between pricing and efficacy. Compared to control groups, immunotherapeutics and drugs targeting oncogenes or angiogenesis improve efficacy to a greater degree than chemotherapy. Immunotherapy appears to have better safety and tolerability profile compared to other cancer therapies. Market price of drugs is not related to efficacy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ascorbic acid enhances oxidative stress tolerance and biological control efficacy of Pichia caribbica against postharvest blue mold decay of apples.

PubMed

Li, Chaolan; Zhang, Hongyin; Yang, Qiya; Komla, Mahunu Gustav; Zhang, Xiaoyun; Zhu, Shuyun

2014-07-30

The effect of ascorbic acid (VC) on improving oxidative stress tolerance of Pichia caribbica and biocontrol efficacy against blue mold caused by Penicillium expansum on apples was investigated. P. caribbica showed susceptibility to the oxidative stress in vitro test, and 250 μg/mL VC treatment improved its oxidative stress tolerance. The higher viability exhibited by VC-treated yeast was associated with a lower intracellular ROS level. The activities of antioxidant enzymes of P. caribbica were improved by VC treatment, including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPX). Additionally, VC-treated yeast exhibited greater biocontrol activity against P. expansum and faster growth when stored at 25 and 4 °C, respectively, compared to the performance of the non-VC-treated yeast. In response to the VC treatment under oxidative stress, several differentially expressed proteins were identified in P. caribbica, and most of the poteins were confirmed to be related to basic metabolism. Therefore, the application of ascorbic acid is a useful approach to improve oxidative stress tolerance of P. caribbica and its biocontrol efficacy on apples.

Comparative transcriptomics elucidates adaptive phenol tolerance and utilization in lipid-accumulating Rhodococcus opacus PD630

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoneda, Aki; Henson, William R.; Goldner, Nicholas K.

Lignin-derived (e.g. phenolic) compounds can compromise the bioconversion of lignocellulosic biomass to fuels and chemicals due to their toxicity and recalcitrance. The lipid-accumulating bacterium Rhodococcus opacus PD630 has recently emerged as a promising microbial host for lignocellulose conversion to value-added products due to its natural ability to tolerate and utilize phenolics. To gain a better understanding of its phenolic tolerance and utilization mechanisms, we adaptively evolved R. opacus over 40 passages using phenol as its sole carbon source (up to 373% growth improvement over wild-type), and extensively characterized two strains from passages 33 and 40. The two adapted strains showedmore » higher phenol consumption rates (~20 mg/l/h) and ~2-fold higher lipid production from phenol than the wild-type strain.Whole-genome sequencing and comparative transcriptomics identified highly-upregulated degradation pathways and putative transporters for phenol in both adapted strains, highlighting the important linkage between mechanisms of regulated phenol uptake, utilization, and evolved tolerance. Our study shows that the R. opacus mutants are likely to use their transporters to import phenol rather than export them, suggesting a new aromatic tolerance mechanism. The identified tolerance genes and pathways are promising candidates for future metabolic engineering in R. opacus for improved lignin conversion to lipid-based products.« less

Comparative transcriptomics elucidates adaptive phenol tolerance and utilization in lipid-accumulating Rhodococcus opacus PD630

DOE PAGES

Yoneda, Aki; Henson, William R.; Goldner, Nicholas K.; ...

2016-02-02

Lignin-derived (e.g. phenolic) compounds can compromise the bioconversion of lignocellulosic biomass to fuels and chemicals due to their toxicity and recalcitrance. The lipid-accumulating bacterium Rhodococcus opacus PD630 has recently emerged as a promising microbial host for lignocellulose conversion to value-added products due to its natural ability to tolerate and utilize phenolics. To gain a better understanding of its phenolic tolerance and utilization mechanisms, we adaptively evolved R. opacus over 40 passages using phenol as its sole carbon source (up to 373% growth improvement over wild-type), and extensively characterized two strains from passages 33 and 40. The two adapted strains showedmore » higher phenol consumption rates (~20 mg/l/h) and ~2-fold higher lipid production from phenol than the wild-type strain.Whole-genome sequencing and comparative transcriptomics identified highly-upregulated degradation pathways and putative transporters for phenol in both adapted strains, highlighting the important linkage between mechanisms of regulated phenol uptake, utilization, and evolved tolerance. Our study shows that the R. opacus mutants are likely to use their transporters to import phenol rather than export them, suggesting a new aromatic tolerance mechanism. The identified tolerance genes and pathways are promising candidates for future metabolic engineering in R. opacus for improved lignin conversion to lipid-based products.« less

Modification of high saturated fat diet with n-3 polyunsaturated fat improves glucose intolerance and vascular dysfunction

PubMed Central

Lamping, KL; Nuno, DW; Coppey, LJ; Holmes, AJ; Hu, S; Oltman, CL; Norris, AW; Yorek, MA

2013-01-01

Aims The ability of dietary enrichment with monounsaturated (MUFA), n-3, or n-6 polyunsaturated fatty acids (PUFA) to reverse glucose intolerance and vascular dysfunction resulting from excessive dietary saturated fatty acids is not resolved. We hypothesized that partial replacement of dietary saturated fats with n-3 PUFA enriched menhaden oil (MO) would provide greater improvement in glucose tolerance and vascular function compared to n-6 enriched safflower oil (SO) or MUFA-enriched olive oil (OO). Material and Methods We fed mice a high saturated fat diet (60% kcal from lard) for 12 weeks before substituting half the lard with MO, SO or OO for an additional 4 weeks. At the end of 4 weeks, we assessed glucose tolerance, insulin signaling and reactivity of isolated pressurized gracilis arteries. Results After 12 weeks of saturated fat diet, body weights were elevated and glucose tolerance abnormal compared to mice on control diet (13% kcal lard). Diet substituted with MO restored basal glucose levels, glucose tolerance, and indices of insulin signaling (phosphorylated Akt) to normal whereas restoration was limited for SO and OO substitutions. Although dilation to acetylcholine was reduced in arteries from mice on HF, OO and SO diets compared to normal diet, dilation to acetylcholine was fully restored and constriction to phenylephrine reduced in MO fed mice compared to normal. Conclusion We conclude that short term enrichment of an ongoing high fat diet with n-3 PUFA rich MO but not MUFA rich OO or n-6 PUFA rich SO reverses glucose tolerance, insulin signaling, and vascular dysfunction. PMID:22950668

Expression of OsMYB55 in maize activates stress-responsive genes and enhances heat and drought tolerance.

PubMed

Casaretto, José A; El-Kereamy, Ashraf; Zeng, Bin; Stiegelmeyer, Suzy M; Chen, Xi; Bi, Yong-Mei; Rothstein, Steven J

2016-04-29

Plant response mechanisms to heat and drought stresses have been considered in strategies for generating stress tolerant genotypes, but with limited success. Here, we analyzed the transcriptome and improved tolerance to heat stress and drought of maize plants over-expressing the OsMYB55 gene. Over-expression of OsMYB55 in maize decreased the negative effects of high temperature and drought resulting in improved plant growth and performance under these conditions. This was evidenced by the higher plant biomass and reduced leaf damage exhibited by the transgenic lines compared to wild type when plants were subjected to individual or combined stresses and during or after recovery from stress. A global transcriptomic analysis using RNA sequencing revealed that several genes induced by heat stress in wild type plants are constitutively up-regulated in OsMYB55 transgenic maize. In addition, a significant number of genes up-regulated in OsMYB55 transgenic maize under control or heat treatments have been associated with responses to abiotic stresses including high temperature, dehydration and oxidative stress. The latter is a common and major consequence of imposed heat and drought conditions, suggesting that this altered gene expression may be associated with the improved stress tolerance in these transgenic lines. Functional annotation and enrichment analysis of the transcriptome also pinpoint the relevance of specific biological processes for stress responses. Our results show that expression of OsMYB55 can improve tolerance to heat stress and drought in maize plants. Enhanced expression of stress-associated genes may be involved in OsMYB55-mediated stress tolerance. Possible implications for the improved tolerance to heat stress and drought of OsMYB55 transgenic maize are discussed.

Difference in oxidative stress tolerance between rice cultivars estimated with chlorophyll fluorescence analysis.

PubMed

Kasajima, Ichiro

2017-04-26

Oxidative stress is considered to be involved in growth retardation of plants when they are exposed to a variety of biotic and abiotic stresses. Despite its potential importance in improving crop production, comparative studies on oxidative stress tolerance between rice (Oryza sativa L.) cultivars are limited. This work describes the difference in term of oxidative stress tolerance between 72 rice cultivars. 72 rice cultivars grown under naturally lit greenhouse were used in this study. Excised leaf discs were subjected to a low concentration of methyl viologen (paraquat), a chemical reagent known to generate reactive oxygen species in chloroplast. Chlorophyll fluorescence analysis using a two-dimensional fluorescence meter, ion leakage analysis as well as the measurement of chlorophyll contents were used to evaluate the oxidative stress tolerance of leaf discs. Furthermore, fluorescence intensities were finely analyzed based on new fluorescence theories that we have optimized. Treatment of leaf discs with methyl viologen caused differential decrease of maximum quantum yield of photosystem II (Fv/Fm) between cultivars. Decrease of Fv/Fm was also closely correlated with increase of ion leakage and decrease of chlorophyll a/b ratio. Fv/Fm was factorized into photochemical and non-photochemical parameters to classify rice cultivars into sensitive and tolerant ones. Among the 72 compared rice cultivars, the traditional cultivar Co13 was identified as the most tolerant to oxidative stress. Koshihikari, a dominant modern Japonica cultivar in Japan as well as IR58, one of the modern Indica breeding lines exhibited a strong tolerance to oxidative stress. Close correlation between Fv/Fm and chlorophyll a/b ratio provides a simple method to estimate oxidative stress tolerance, without measurement of chlorophyll fluorescence with special equipment. The fact that modern cultivars, especially major cultivars possessed tolerance to oxidative stress suggests that oxidative stress tolerance is one of the agricultural traits prerequisite for improvement of modern rice cultivars. Data presented in this study would enable breeding of rice cultivars having strong tolerance to oxidative stress.

Drought tolerance and proteomics studies of transgenic wheat containing the maize C4 phosphoenolpyruvate carboxylase (PEPC) gene.

PubMed

Qin, Na; Xu, Weigang; Hu, Lin; Li, Yan; Wang, Huiwei; Qi, Xueli; Fang, Yuhui; Hua, Xia

2016-11-01

Enhancing drought tolerance of crops has been a great challenge in crop improvement. Here, we report the maize phosphoenolpyruvate carboxylase (PEPC) gene was able to confer drought tolerance and increase grain yield in transgenic wheat (Triticum aestivum L.) plants. The improved of drought tolerance was associated with higher levels of proline, soluble sugar, soluble protein, and higher water use efficiency. The transgenic wheat plants had also a more extensive root system as well as increased photosynthetic capacity during stress treatments. The increased grain yield of the transgenic wheat was contributed by improved biomass, larger spike and grain numbers, and heavier 1000-grain weight under drought-stress conditions. Under non-stressed conditions, there were no significant increases in these of the measured traits except for photosynthetic rate when compared with parental wheat. Proteomic research showed that the expression levels of some proteins, including chlorophyll A-B binding protein and pyruvate, phosphate dikinase, which are related to photosynthesis, PAP fibrillin, which is involved in cytoskeleton synthesis, S-adenosylmethionine synthetase, which catalyzes methionine synthesis, were induced in the transgenic wheat under drought stress. Additionally, the expression of glutamine synthetase, which is involved in ammonia assimilation, was induced by drought stress in the wheat. Our study shows that PEPC can improve both stress tolerance and grain yield in wheat, demonstrating the efficacy of PEPC in crop improvement.

Newly Identified Wild Rice Accessions Conferring High Salt Tolerance Might Use a Tissue Tolerance Mechanism in Leaf.

PubMed

Prusty, Manas R; Kim, Sung-Ryul; Vinarao, Ricky; Entila, Frederickson; Egdane, James; Diaz, Maria G Q; Jena, Kshirod K

2018-01-01

Cultivated rice ( Oryza sativa L.) is very sensitive to salt stress. So far a few rice landraces have been identified as a source of salt tolerance and utilized in rice improvement. These tolerant lines primarily use Na + exclusion mechanism in root which removes Na + from the xylem stream by membrane Na + and K + transporters, and resulted in low Na + accumulation in shoot. Identification of a new donor source conferring high salt tolerance is imperative. Wild relatives of rice having wide genetic diversity are regarded as a potential source for crop improvement. However, they have been less exploited against salt stress. Here, we simultaneously evaluated all 22 wild Oryza species along with the cultivated tolerant lines including Pokkali, Nona Bokra, and FL478, and sensitive check varieties under high salinity (240 mM NaCl). Based on the visual salt injury score, three species ( O . alta, O . latifolia , and O . coarctata ) and four species ( O . rhizomatis, O . eichingeri, O . minuta , and O . grandiglumis ) showed higher and similar level of tolerance compared to the tolerant checks, respectively. All three CCDD genome species exhibited salt tolerance, suggesting that the CCDD genome might possess the common genetic factors for salt tolerance. Physiological and biochemical experiments were conducted using the newly isolated tolerant species together with checks under 180 mM NaCl. Interestingly, all wild species showed high Na + concentration in shoot and low concentration in root unlike the tolerant checks. In addition, the wild-tolerant accessions showed a tendency of a high tissue tolerance in leaf, low malondialdehyde level in shoot, and high retention of chlorophyll in the young leaves. These results suggest that the wild species employ tissue tolerance mechanism to manage salt stress. Gene expression analyses of the key salt tolerance-related genes suggested that high Na + in leaf of wild species might be affected by OsHKT1;4 -mediated Na + exclusion in leaf and the following Na + sequestration in leaf might be occurring independent of tonoplast-localized OsNHX1. The newly isolated wild rice accessions will be valuable materials for both rice improvement to salinity stress and the study of salt tolerance mechanism in plants.

A Novel Dual Separate Paths (DSP) Algorithm Providing Fault-Tolerant Communication for Wireless Sensor Networks.

PubMed

Tien, Nguyen Xuan; Kim, Semog; Rhee, Jong Myung; Park, Sang Yoon

2017-07-25

Fault tolerance has long been a major concern for sensor communications in fault-tolerant cyber physical systems (CPSs). Network failure problems often occur in wireless sensor networks (WSNs) due to various factors such as the insufficient power of sensor nodes, the dislocation of sensor nodes, the unstable state of wireless links, and unpredictable environmental interference. Fault tolerance is thus one of the key requirements for data communications in WSN applications. This paper proposes a novel path redundancy-based algorithm, called dual separate paths (DSP), that provides fault-tolerant communication with the improvement of the network traffic performance for WSN applications, such as fault-tolerant CPSs. The proposed DSP algorithm establishes two separate paths between a source and a destination in a network based on the network topology information. These paths are node-disjoint paths and have optimal path distances. Unicast frames are delivered from the source to the destination in the network through the dual paths, providing fault-tolerant communication and reducing redundant unicast traffic for the network. The DSP algorithm can be applied to wired and wireless networks, such as WSNs, to provide seamless fault-tolerant communication for mission-critical and life-critical applications such as fault-tolerant CPSs. The analyzed and simulated results show that the DSP-based approach not only provides fault-tolerant communication, but also improves network traffic performance. For the case study in this paper, when the DSP algorithm was applied to high-availability seamless redundancy (HSR) networks, the proposed DSP-based approach reduced the network traffic by 80% to 88% compared with the standard HSR protocol, thus improving network traffic performance.

Comparison of genome-wide selection strategies to identify furfural tolerance genes in Escherichia coli.

PubMed

Glebes, Tirzah Y; Sandoval, Nicholas R; Gillis, Jacob H; Gill, Ryan T

2015-01-01

Engineering both feedstock and product tolerance is important for transitioning towards next-generation biofuels derived from renewable sources. Tolerance to chemical inhibitors typically results in complex phenotypes, for which multiple genetic changes must often be made to confer tolerance. Here, we performed a genome-wide search for furfural-tolerant alleles using the TRackable Multiplex Recombineering (TRMR) method (Warner et al. (2010), Nature Biotechnology), which uses chromosomally integrated mutations directed towards increased or decreased expression of virtually every gene in Escherichia coli. We employed various growth selection strategies to assess the role of selection design towards growth enrichments. We also compared genes with increased fitness from our TRMR selection to those from a previously reported genome-wide identification study of furfural tolerance genes using a plasmid-based genomic library approach (Glebes et al. (2014) PLOS ONE). In several cases, growth improvements were observed for the chromosomally integrated promoter/RBS mutations but not for the plasmid-based overexpression constructs. Through this assessment, four novel tolerance genes, ahpC, yhjH, rna, and dicA, were identified and confirmed for their effect on improving growth in the presence of furfural. © 2014 Wiley Periodicals, Inc.

Modifications of Antiepileptic Drugs for Improved Tolerability and Efficacy

PubMed Central

Landmark, Cecilie Johannessen; Johannessen, Svein I.

2008-01-01

Introduction A large number of antiepileptic drugs (AEDs) are available today, but they may not be satisfactory regarding clinical efficacy, tolerance, toxicity or pharmacokinetic properties. The purpose of this review is to focus upon the rationale behind the chemical modifications of several recently marketed AEDs or drugs in development and to categorize them according to the main purposes for the improvements: better efficacy or tolerability accompanied by improved pharmacokinetic properties. Material and Method AEDs that have been chemically modified to new derivatives during the last years are reviewed based on recent publications and PubMed-searches. Results and Discussion Improvement in pharmacokinetic parameters may affect both tolerability and efficacy. Modifications to improve tolerability include various valproate analogues, divided into aliphatic amides, cyclic derivatives or amino acid conjugates. Furthermore, there are the carbamazepine analogues oxcarbazepine and eslicarbazepine, the felbamate analogues fluorofelbamate and carisbamate (RWJ 33369), and the lamotrigine analogue JZP-4. The levetiracetam analogues brivaracetam and seletracetam and the derivatives of gabapentin, pregabalin and XP13512, have improved selectivity compared to their parent compounds. Other new drugs have new mechanisms of action related to GABA and glutamate receptors; the glutamate antagonists like topiramate (talampanel and NS-1209), and GABAA receptor agonists, benzodiazepine or progesterone analogues (ELB-139 and ganaxolone). Conclusion Further challenges for development of new AEDs include investigations of target molecules affected by pathophysiological processes and detailed structure-activity relationships with focus on stereoselectivity. These potential drugs may become of importance in future drug therapy in epilepsy and other CNS disorders. PMID:19787095

Improving salinity tolerance of plants through conventional breeding and genetic engineering: An analytical comparison.

PubMed

Ashraf, Muhammad; Akram, Nudrat Aisha

2009-01-01

The last century has witnessed a substantial improvement in yield potential, quality and disease resistance in crops. This was indeed the outcome of conventional breeding, which was achieved with little or no knowledge of underlying physiological and biochemical phenomena related to a trait. Also the resources utilized on programs involving conventional breeding were not of great magnitude. Plant breeders have also been successful during the last century in producing a few salt-tolerant cultivars/lines of some potential crops through conventional breeding, but this again has utilized modest resources. However, this approach seems now inefficient due to a number of reasons, and alternatively, genetic engineering for improving crop salt tolerance is being actively followed these days by the plant scientists, world-over. A large number of transgenic lines with enhanced salt tolerance of different crops can be deciphered from the literature but up to now only a very few field-tested cultivars/lines are known despite the fact that considerable resources have been expended on the sophisticated protocols employed for generating such transgenics. This review analytically compares the achievements made so far in terms of producing salt-tolerant lines/cultivars through conventional breeding or genetic engineering.

Absence of Rtt109p, a fungal-specific histone acetyltransferase, results in improved acetic acid tolerance of Saccharomyces cerevisiae.

PubMed

Cheng, Cheng; Zhao, Xinqing; Zhang, Mingming; Bai, Fengwu

2016-03-01

RTT109 is a histone acetyltransferase for the acetylation of histone H3. It is still not clear whether RTT109 plays a role in regulation of gene expression under environmental stresses. In this study, the involvement of RTT109 in acetic acid stress tolerance of Saccharomyces cerevisiae was investigated. It was revealed that the absence of RTT109 enhanced resistance to 5.5 g L(-1) acetic acid, which was indicated by improved growth of RTT109Δ mutant compared with that of the wild-type BY4741 strain. Meanwhile, the lag phase was shortened for 48 h and glucose consumption completed 36 h in advance for RTT109Δ mutant compared to the wild-type strain, with ethanol production rate increased from 0.39 to 0.60 g L(-1) h(-1). Significantly, elevated transcription levels of HSP12, CTT1 and GSH1, as well as increased activities of antioxidant enzymes were observed in RTT109Δ under acetic acid stress. Improved flocculation of RTT109Δ compared to that of the control strain BY4741 under the acetic acid stress was also observed. These results suggest that the absence of RTT109 not only activates transcription of stress responsive genes, but also improves resistance to oxidative stress, which ultimately contributes to improved acetic acid tolerance in S. cerevisiae. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Understanding of how Propionibacterium acidipropionici respond to propionic acid stress at the level of proteomics

PubMed Central

Guan, Ningzi; Shin, Hyun-dong; Chen, Rachel R.; Li, Jianghua; Liu, Long; Du, Guocheng; Chen, Jian

2014-01-01

Propionic acid (PA) is an important platform chemical in the food, agriculture, and pharmaceutical industries and is mainly biosynthesized by propionibacteria. Acid tolerance in PA-producing strains is crucial. In previous work, we investigated the acid tolerance mechanism of Propionibacterium acidipropionici at microenvironmental levels by analyzing physiological changes in the parental strain and three PA-tolerant mutants obtained by genome shuffling. However, the molecular mechanism of PA tolerance in P. acidipropionici remained unclear. Here, we performed a comparative proteomics study of P. acidipropionici CGMCC 1.2230 and the acid-tolerant mutant P. acidipropionici WSH1105; MALDI-TOF/MS identified 24 proteins that significantly differed between the parental and shuffled strains. The differentially expressed proteins were mainly categorized as key components of crucial biological processes and the acid stress response. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was used to confirm differential expression of nine key proteins. Overexpression of the secretory protein glyceraldehyde-3-phosphate dehydrogenase and ATP synthase subunit α in Escherichia coli BL21 improved PA and acetic acid tolerance; overexpression of NADH dehydrogenase and methylmalonyl-CoA epimerase improved PA tolerance. These results provide new insights into the acid tolerance of P. acidipropionici and will facilitate the development of PA production through fermentation by propionibacteria. PMID:25377721

Simultaneous Expression of PDH45 with EPSPS Gene Improves Salinity and Herbicide Tolerance in Transgenic Tobacco Plants

PubMed Central

Garg, Bharti; Gill, Sarvajeet S.; Biswas, Dipul K.; Sahoo, Ranjan K.; Kunchge, Nandkumar S.; Tuteja, Renu; Tuteja, Narendra

2017-01-01

To cope with the problem of salinity- and weed-induced crop losses, a multi-stress tolerant trait is need of the hour but a combinatorial view of such traits is not yet explored. The overexpression of PDH45 (pea DNA helicase 45) and EPSPS (5-enoylpruvyl shikimate-3-phosphate synthase) genes have been reported to impart salinity and herbicide tolerance. Further, the understanding of mechanism and pathways utilized by PDH45 and EPSPS for salinity and herbicide tolerance will help to improve the crops of economical importance. In the present study, we have performed a comparative analysis of salinity and herbicide tolerance to check the biochemical parameters and antioxidant status of tobacco transgenic plants. Collectively, the results showed that PDH45 overexpressing transgenic lines display efficient tolerance to salinity stress, while PDH45+EPSPS transgenics showed tolerance to both the salinity and herbicide as compared to the control [wild type (WT) and vector control (VC)] plants. The activities of the components of enzymatic antioxidant machinery were observed to be higher in the transgenic plants indicating the presence of an efficient antioxidant defense system which helps to cope with the stress-induced oxidative-damages. Photosynthetic parameters also showed significant increase in PDH45 and PDH45+EPSPS overexpressing transgenic plants in comparison to WT, VC and EPSPS transgenic plants under salinity stress. Furthermore, PDH45 and PDH45+EPSPS synergistically modulate the jasmonic acid and salicylic acid mediated signaling pathways for combating salinity stress. The findings of our study suggest that pyramiding of the PDH45 gene with EPSPS gene renders host plants tolerant to salinity and herbicide by enhancing the antioxidant machinery thus photosynthesis. PMID:28392794

Improved drought tolerance in wheat plants overexpressing a synthetic bacterial cold shock protein gene SeCspA

PubMed Central

Yu, Tai-Fei; Xu, Zhao-Shi; Guo, Jin-Kao; Wang, Yan-Xia; Abernathy, Brian; Fu, Jin-Dong; Chen, Xiao; Zhou, Yong-Bin; Chen, Ming; Ye, Xing-Guo; Ma, You-Zhi

2017-01-01

Cold shock proteins (CSPs) enhance acclimatization of bacteria to adverse environmental circumstances. The Escherichia coli CSP genes CspA and CspB were modified to plant-preferred codon sequences and named as SeCspA and SeCspB. Overexpression of exogenous SeCspA and SeCspB in transgenic Arabidopsis lines increased germination rates, survival rates, and increased primary root length compared to control plants under drought and salt stress. Investigation of several stress-related parameters in SeCspA and SeCspB transgenic wheat lines indicated that these lines possessed stress tolerance characteristics, including lower malondialdehyde (MDA) content, lower water loss rates, lower relative Na+ content, and higher chlorophyll content and proline content than the control wheat plants under drought and salt stresses. RNA-seq and qRT-PCR expression analysis showed that overexpression of SeCsp could enhance the expression of stress-responsive genes. The field experiments showed that the SeCspA transgenic wheat lines had great increases in the 1000-grain weight and grain yield compared to the control genotype under drought stress conditions. Significant differences in the stress indices revealed that the SeCspA transgenic wheat lines possessed significant and stable improvements in drought tolerance over the control plants. No such improvement was observed for the SeCspB transgenic lines under field conditions. Our results indicated that SeCspA conferred drought tolerance and improved physiological traits in wheat plants. PMID:28281578

Identification and Characterization of an Arabidopsis thaliana Mutant lbt With High Tolerance to Boron Deficiency

PubMed Central

Huai, Zexun; Peng, Lishun; Wang, Sheliang; Zhao, Hua; Shi, Lei; Xu, Fangsen

2018-01-01

Boron (B) is an essential micronutrient of plants. In the present study, we characterized an Arabidopsis mutant lbt with significant low-boron tolerance that was identified based on our previous mapping of QTL for B efficiency in Arabidopsis. Multiple nutrient-deficiency analyses point out that lbt mutant is insensitive to only B-limitation stress. Compared with wild-type Col-0, the fresh weight, leaf area, root length and root elongation rate of lbt mutant were significantly improved under B deficiency during vegetative growth. lbt mutant also showed the improvements in plant height, branches and inflorescences compared with Col-0 during the reproductive stage under B limitation. Ultrastructure analysis of the leaves showed that starch accumulation in lbt mutant was significantly diminished compared with Col-0. Furthermore, there were no significant differences in the expression of transporter-related genes and B concentrations between Col-0 and lbt mutant under both normal B and low-B conditions. These results suggest that lbt mutant has a lower B demand than Col-0. Genetic analysis suggests that the low-B tolerant phenotype of lbt mutant is under the control of a monogenic recessive gene. Based on the high-density SNP linkage genetic map, only one QTL for low-B tolerance was mapped on chromosome 4 between 10.4 and 14.8 Mb. No any reported B-relative genes exist in the QTL interval, suggesting that a gene with unknown function controls the tolerance of lbt to B limitation. Taken together, lbt is a low-B tolerant mutant that does not depend on the uptake or transport of B and is controlled by a monogenic recessive gene mapped on chromosome 4, and cloning and functional analysis of LBT gene are expected to reveal novel mechanisms for plant resistance to B deficiency.

Salt stress-induced changes in antioxidative defense system and proteome profiles of salt-tolerant and sensitive Frankia strains.

PubMed

Srivastava, Amrita; Singh, Anumeha; Singh, Satya S; Mishra, Arun K

2017-04-16

An appreciation of comparative microbial survival is most easily done while evaluating their adaptive strategies during stress. In the present experiment, antioxidative and whole cell proteome variations based on spectrophotometric analysis and SDS-PAGE and 2-dimensional gel electrophoresis have been analysed among salt-tolerant and salt-sensitive Frankia strains. This is the first report of proteomic basis underlying salt tolerance in these newly isolated Frankia strains from Hippophae salicifolia D. Don. Salt-tolerant strain HsIi10 shows higher increment in the contents of superoxide dismutase, catalase and ascorbate peroxidase as compared to salt-sensitive strain HsIi8. Differential 2-DGE profile has revealed differential profiles for salt-tolerant and salt-sensitive strains. Proteomic confirmation of salt tolerance in the strains with inbuilt efficiency of thriving in nitrogen-deficient locales is a definite advantage for these microbes. This would be equally beneficial for improvement of soil nitrogen status. Efficient protein regulation in HsIi10 suggests further exploration for its potential use as biofertilizer in saline soils.

Comparative Proteomic Analysis of Aluminum Tolerance in Tibetan Wild and Cultivated Barleys

PubMed Central

Dai, Huaxin; Cao, Fangbin; Chen, Xianhong; Zhang, Mian; Ahmed, Imrul Mosaddek; Chen, Zhong-Hua; Li, Chengdao; Zhang, Guoping; Wu, Feibo

2013-01-01

Aluminum (Al) toxicity is a major limiting factor for plant production in acid soils. Wild barley germplasm is rich in genetic diversity and may provide elite genes for crop Al tolerance improvement. The hydroponic-experiments were performed to compare proteomic and transcriptional characteristics of two contrasting Tibetan wild barley genotypes Al- resistant/tolerant XZ16 and Al-sensitive XZ61 as well as Al-resistant cv. Dayton. Results showed that XZ16 had less Al uptake and translocation than XZ61 and Dayton under Al stress. Thirty-five Al-tolerance/resistance-associated proteins were identified and categorized mainly in metabolism, energy, cell growth/division, protein biosynthesis, protein destination/storage, transporter, signal transduction, disease/defense, etc. Among them, 30 were mapped on barley genome, with 16 proteins being exclusively up-regulated by Al stress in XZ16, including 4 proteins (S-adenosylmethionine-synthase 3, ATP synthase beta subunit, triosephosphate isomerase, Bp2A) specifically expressed in XZ16 but not Dayton. The findings highlighted the significance of specific-proteins associated with Al tolerance, and verified Tibetan wild barley as a novel genetic resource for Al tolerance. PMID:23691047

Development and Event-specific Detection of Transgenic Glyphosate-resistant Rice Expressing the G2-EPSPS Gene

PubMed Central

Dong, Yufeng; Jin, Xi; Tang, Qiaoling; Zhang, Xin; Yang, Jiangtao; Liu, Xiaojing; Cai, Junfeng; Zhang, Xiaobing; Wang, Xujing; Wang, Zhixing

2017-01-01

Glyphosate is a widely used herbicide, due to its broad spectrum, low cost, low toxicity, high efficiency, and non-selective characteristics. Rice farmers rarely use glyphosate as a herbicide, because the crop is sensitive to this chemical. The development of transgenic glyphosate-tolerant rice could greatly improve the economics of rice production. Here, we transformed the Pseudomonas fluorescens G2 5-enolpyruvyl shikimate-3-phosphate synthase (EPSPS) gene G2-EPSPS, which conferred tolerance to glyphosate herbicide into a widely used japonica rice cultivar, Zhonghua 11 (ZH11), to develop two highly glyphosate-tolerant transgenic rice lines, G2-6 and G2-7, with one exogenous gene integration. Seed germination tests and glyphosate-tolerance assays of plants grown in a greenhouse showed that the two transgenic lines could greatly improve glyphosate-tolerance compared with the wild-type; The glyphosate-tolerance field test indicated that both transgenic lines could grow at concentrations of 20,000 ppm glyphosate, which is more than 20-times the recommended concentration in the field. Isolation of the flanking sequence of transgenic rice G2-6 indicated that the 5′-terminal of T-DNA was inserted into chromosome 8 of the rice genome. An event-specific PCR test system was established and the limit of detection of the primers reached five copies. Overall, the G2-EPSPS gene significantly improved glyphosate-tolerance in transgenic rice; furthermore, it is a useful candidate gene for the future development of commercial transgenic rice. PMID:28611804

Leveraging Genetic-Background Effects in Saccharomyces cerevisiae To Improve Lignocellulosic Hydrolysate Tolerance

DOE PAGES

Sardi, Maria; Rovinskiy, Nikolay; Zhang, Yaoping; ...

2016-07-22

We report a major obstacle to sustainable lignocellulosic biofuel production is microbe inhibition by the combinatorial stresses in pretreated plant hydrolysate. Chemical biomass pretreatment releases a suite of toxins that interact with other stressors, including high osmolarity and temperature, which together can have poorly understood synergistic effects on cells. Improving tolerance in industrial strains has been hindered, in part because the mechanisms of tolerance reported in the literature often fail to recapitulate in other strain backgrounds. Here, we explored and then exploited variations in stress tolerance, toxin-induced transcriptomic responses, and fitness effects of gene overexpression in different Saccharomyces cerevisiae (yeast)more » strains to identify genes and processes linked to tolerance of hydrolysate stressors. Using six different S. cerevisiae strains that together maximized phenotypic and genetic diversity, first we explored transcriptomic differences between resistant and sensitive strains to identify common and strain-specific responses. This comparative analysis implicated primary cellular targets of hydrolysate toxins, secondary effects of defective defense strategies, and mechanisms of tolerance. Dissecting the responses to individual hydrolysate components across strains pointed to synergistic interactions between osmolarity, pH, hydrolysate toxins, and nutrient composition. By characterizing the effects of high-copy gene overexpression in three different strains, we revealed the breadth of the background-specific effects of gene fitness contributions in synthetic hydrolysate. Lastly, our approach identified new genes for engineering improved stress tolerance in diverse strains while illuminating the effects of genetic background on molecular mechanisms.« less

Improved irradiation tolerance of reactive gas pulse sputtered TiN coatings with a hybrid architecture of multilayered and compositionally graded structures

NASA Astrophysics Data System (ADS)

Liang, Wei; Yang, Jijun; Zhang, Feifei; Lu, Chenyang; Wang, Lumin; Liao, Jiali; Yang, Yuanyou; Liu, Ning

2018-04-01

This study investigates the improved irradiation tolerance of reactive gas pulse (RGP) sputtered TiN coatings which has hybrid architecture of multilayered and compositionally graded structures. The multilayered RGP-TiN coating is composed of hexagonal close-packed Ti phase and face-centred cubic TiN phase sublayers, where the former sublayer has a compositionally graded structure and the latter one maintains constant stoichiometric atomic ratio of Ti:N. After 100 keV He ion irradiation, the RGP-TiN coating exhibits improved irradiation resistance compared with its single layered (SL) counterpart. The size and density of He bubbles are smaller in the RGP-TiN coating than in the SL-TiN coating. The irradiation-induced surface blistering of the coatings shows a similar tendency. Meanwhile, the irradiation hardening and adhesion strength of the RGP-TiN coatings were not greatly affected by He irradiation. Moreover, the irradiation damage tolerance of the coatings can be well tuned by changing the undulation period number of N2 gas flow rate. Detailed analysis suggested that this improved irradiation tolerance could be related to the combined contribution of the multilayered and compositionally graded structures.

Comparative mapping of quantitative trait loci associated with waterlogging tolerance in barley (Hordeum vulgare L.).

PubMed

Li, Haobing; Vaillancourt, René; Mendham, Neville; Zhou, Meixue

2008-08-27

Resistance to soil waterlogging stress is an important plant breeding objective in high rainfall or poorly drained areas across many countries in the world. The present study was conducted to identify quantitative trait loci (QTLs) associated with waterlogging tolerance (e.g. leaf chlorosis, plant survival and biomass reduction) in barley and compare the QTLs identified across two seasons and in two different populations using a composite map constructed with SSRs, RFLP and Diversity Array Technology (DArT) markers. Twenty QTLs for waterlogging tolerance related traits were found in the two barley double haploid (DH) populations. Several of these QTLs were validated through replication of experiments across seasons or by co-location across populations. Some of these QTLs affected multiple waterlogging tolerance related traits, for example, QTL Qwt4-1 contributed not only to reducing barley leaf chlorosis, but also increasing plant biomass under waterlogging stress, whereas other QTLs controlled both leaf chlorosis and plant survival. Improving waterlogging tolerance in barley is still at an early stage compared with other traits. QTLs identified in this study have made it possible to use marker assisted selection (MAS) in combination with traditional field selection to significantly enhance barley breeding for waterlogging tolerance. There may be some degree of homoeologous relationship between QTLs controlling barley waterlogging tolerance and that in other crops as discussed in this study.

Overexpression of SeNHX1 improves both salt tolerance and disease resistance in tobacco.

PubMed

Chen, Xianyang; Bao, Hexigeduleng; Guo, Jie; Jia, Weitao; Li, Yinxin

2015-01-01

Recently, we found NHX1, the gene encoding a Na(+)/H(+) exchanger, participated in plant disease defense. Although NHX1 has been confirmed to be involved in plant salt tolerance, whether the NHX1 transgenic plants exhibit both salt tolerance and disease resistance has not been investigated. The T1 progenies of Nicotiana tabacum L. lines expressing SeNHX1 (from Salicornia europaea) were generated for the present study. Compared with PBI-type control plants, SeNHX1 transgenic tobaccos exhibited more biomass, longer root length, and higher K(+)/Na(+) ratio at post germination or seedling stage under NaCl treatment, indicating enhanced salt tolerance. The vacuolar H(+) efflux in SeNHX1 transgenic tobacco was increased after treatment of NaCl with different concentration. Meanwhile, the SeNHX1 transgenic tobaccos showed smaller wilted spot area, less H2O2 accumulation in leaves after infection of Phytophthora parasitica var. nicotianae. Further investigation demonstrated a larger NAD(P)(H) pool in SeNHX1 transgenic tobacco. These evidences revealed that overexpression of SeNHX1 intensified the compartmentation of Na(+) into vacuole under salt stress and improved the ability of eliminating ROS after pathogen attack, which then enhanced salt tolerance and disease resistance simultaneously in tobacco. Our findings indicate NHX1 has potential value in creating crops with both improved salt tolerance and disease resistance.

Coffee and caffeine improve insulin sensitivity and glucose tolerance in C57BL/6J mice fed a high-fat diet.

PubMed

Matsuda, Yuji; Kobayashi, Misato; Yamauchi, Rie; Ojika, Makoto; Hiramitsu, Masanori; Inoue, Takashi; Katagiri, Takao; Murai, Atsushi; Horio, Fumihiko

2011-01-01

We have previously demonstrated that coffee and caffeine ameliorated hyperglycemia in spontaneously diabetic KK-A(y) mice. This present study evaluates the antidiabetic effects of coffee and caffeine on high-fat-diet-induced impaired glucose tolerance in C57BL/6J mice. C57BL/6J mice fed a high-fat diet were given regular drinking water (control group), or a 2.5-fold-diluted coffee or caffeine solution (200 mg/L) for 17 weeks. The ingestion of coffee or caffeine improved glucose tolerance, insulin sensitivity, and hyperinsulinemia when compared with mice in the control group. The adipose tissue mRNA levels of inflammatory adipocytokines (MCP-1 and IL-6) and the liver mRNA levels of genes related to fatty acid synthesis were lower in the coffee and caffeine groups than those in the control group. These results suggest that coffee and caffeine exerted an ameliorative effect on high-fat-diet-induced impaired glucose tolerance by improving insulin sensitivity. This effect might be attributable in part to the reduction of inflammatory adipocytokine expression.

Longitudinal analysis of the effect of academic failure tolerance on academic achievement fluctuation in medical school students.

PubMed

Chae, Su Jin; Kim, Miran; Chang, Ki Hong

2016-03-01

Academic failure tolerance (AFT) is one of the important psychological concepts in education, but its applications in medical education are rare. Thus, the purpose of this study was to investigate the effect of academic failure tolerance on academic achievement fluctuation among medical school students using a longitudinal research design. The subjects were 43 medical students who responded to the AFT test. This study analyzed the longitudinal data of achievement scores up to the 2nd academic year (2012-2013) among students who were divided into academic achievement improvement and decline groups. Comparing the improvement and decline groups' mean academic achievement fluctuation scores demonstrated that behavior and preferred task difficulty showed high scores whereas feeling scores were lower in the improvement group (p<0.05). In the improvement group, despite the higher negative feeling scores during academic failure, the students favored the more difficult subjects and were more assiduous in their studies. This will form an important basis for enhancing academic achievement among medical students.

Alumina additions may improve the damage tolerance of soft machined zirconia-based ceramics.

PubMed

Oilo, Marit; Tvinnereim, Helene M; Gjerdet, Nils Roar

2011-01-01

The aim of this study was to evaluate the damage tolerance of different zirconia-based materials. Bars of one hard machined and one soft machined dental zirconia and an experimental 95% zirconia 5% alumina ceramic were subjected to 100,000 stress cycles (n = 10), indented to provoke cracks on the tensile stress side (n = 10), and left untreated as controls (n = 10). The experimental material demonstrated a higher relative damage tolerance, with a 40% reduction compared to 68% for the hard machined zirconia and 84% for the soft machined zirconia.

Newly Identified Wild Rice Accessions Conferring High Salt Tolerance Might Use a Tissue Tolerance Mechanism in Leaf

PubMed Central

Prusty, Manas R.; Kim, Sung-Ryul; Vinarao, Ricky; Entila, Frederickson; Egdane, James; Diaz, Maria G. Q.; Jena, Kshirod K.

2018-01-01

Cultivated rice (Oryza sativa L.) is very sensitive to salt stress. So far a few rice landraces have been identified as a source of salt tolerance and utilized in rice improvement. These tolerant lines primarily use Na+ exclusion mechanism in root which removes Na+ from the xylem stream by membrane Na+ and K+ transporters, and resulted in low Na+ accumulation in shoot. Identification of a new donor source conferring high salt tolerance is imperative. Wild relatives of rice having wide genetic diversity are regarded as a potential source for crop improvement. However, they have been less exploited against salt stress. Here, we simultaneously evaluated all 22 wild Oryza species along with the cultivated tolerant lines including Pokkali, Nona Bokra, and FL478, and sensitive check varieties under high salinity (240 mM NaCl). Based on the visual salt injury score, three species (O. alta, O. latifolia, and O. coarctata) and four species (O. rhizomatis, O. eichingeri, O. minuta, and O. grandiglumis) showed higher and similar level of tolerance compared to the tolerant checks, respectively. All three CCDD genome species exhibited salt tolerance, suggesting that the CCDD genome might possess the common genetic factors for salt tolerance. Physiological and biochemical experiments were conducted using the newly isolated tolerant species together with checks under 180 mM NaCl. Interestingly, all wild species showed high Na+ concentration in shoot and low concentration in root unlike the tolerant checks. In addition, the wild-tolerant accessions showed a tendency of a high tissue tolerance in leaf, low malondialdehyde level in shoot, and high retention of chlorophyll in the young leaves. These results suggest that the wild species employ tissue tolerance mechanism to manage salt stress. Gene expression analyses of the key salt tolerance-related genes suggested that high Na+ in leaf of wild species might be affected by OsHKT1;4-mediated Na+ exclusion in leaf and the following Na+ sequestration in leaf might be occurring independent of tonoplast-localized OsNHX1. The newly isolated wild rice accessions will be valuable materials for both rice improvement to salinity stress and the study of salt tolerance mechanism in plants. PMID:29740456

Enhanced Glucose Control Following Vertical Sleeve Gastrectomy Does Not Require a β-Cell Glucagon-Like Peptide 1 Receptor.

PubMed

Douros, Jonathan D; Lewis, Alfor G; Smith, Eric P; Niu, JingJing; Capozzi, Megan; Wittmann, April; Campbell, Jonathan; Tong, Jenny; Wagner, Constance; Mahbod, Parinaz; Seeley, Randy; D'Alessio, David A

2018-05-14

Bariatric surgeries, including vertical sleeve gastrectomy (VSG), resolve diabetes in 40-50% of patients. Studies examining the molecular mechanisms underlying this effect have centered on the role of the insulinotropic glucagon-like peptide 1 (GLP-1), in great part because of the ∼10-fold rise in its circulating levels after surgery. However, there is currently debate over the role of direct β-cell signaling by GLP-1 to mediate improved glucose tolerance following surgery. In order to assess the importance of β-cell GLP-1 receptor (GLP-1R) for improving glucose control after VSG, a mouse model of this procedure was developed and combined with a genetically modified mouse line allowing an inducible, β-cell specific Glp1r knockdown ( Glp1r β-cell-ko ). Mice with VSG lost ∼20% of body weight over 30 days compared to sham-operated controls and had a ∼60% improvement in glucose tolerance. Isolated islets from VSG mice had significantly greater insulin responses to glucose than controls. Glp1r knockdown in β-cells caused glucose intolerance in diet-induced obese mice compared to obese controls, but VSG improved glycemic profiles to similar levels during oral and intraperitoneal glucose challenges in Glp1r βcell-ko and Glp1r WT mice. Therefore, while the β-cell GLP-1R seems to be important for maintaining glucose tolerance in obese mice, in these experiments it is dispensable for the improvement in glucose tolerance after VSG. Moreover, the metabolic physiology activated by VSG can overcome the deficits in glucose regulation caused by lack of β-cell GLP-1 signaling in obesity. © 2018 by the American Diabetes Association.

Co-expression of NCED and ALO improves vitamin C level and tolerance to drought and chilling in transgenic tobacco and stylo plants.

PubMed

Bao, Gegen; Zhuo, Chunliu; Qian, Chunmei; Xiao, Ting; Guo, Zhenfei; Lu, Shaoyun

2016-01-01

Abscisic acid (ABA) regulates plant adaptive responses to various environmental stresses, while L-ascorbic acid (AsA) that is also named vitamin C is an important antioxidant and involves in plant stress tolerance and the immune system in domestic animals. Transgenic tobacco (Nicotiana tabacum L.) and stylo [Stylosanthes guianensis (Aublet) Swartz], a forage legume, plants co-expressing stylo 9-cis-epoxycarotenoid dioxygenase (SgNCED1) and yeast D-arabinono-1,4-lactone oxidase (ALO) genes were generated in this study, and tolerance to drought and chilling was analysed in comparison with transgenic tobacco overexpressing SgNCED1 or ALO and the wild-type plants. Compared to the SgNCED1 or ALO transgenic plants, in which only ABA or AsA levels were increased, both ABA and AsA levels were increased in transgenic tobacco and stylo plants co-expressing SgNCED1 and ALO genes. Compared to the wild type, an enhanced drought tolerance was observed in SgNCED1 transgenic tobacco plants with induced expression of drought-responsive genes, but not in ALO plants, while an enhanced chilling tolerance was observed in ALO transgenic tobaccos with induced expression of cold-responsive genes, but not in SgNCED1 plants. Co-expression of SgNCED1 and ALO genes resulted in elevated tolerance to both drought and chilling in transgenic tobacco and stylo plants with induced expression of both drought and cold-responsive genes. Our result suggests that co-expression of SgNCED1 and ALO genes is an effective way for use in forage plant improvement for increased tolerance to drought and chilling and nutrition quality. © 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

Co-morbid pain and opioid addiction: Long term effect of opioid maintenance on acute pain

PubMed Central

Wachholtz, Amy; Gonzalez, Gerardo

2014-01-01

Introduction Medication assisted treatment for opioid dependence alters the pain experience. This study will evaluate changes pain sensitivity and tolerance with opioid treatments; and duration of this effect after treatment cessation. Method 120 individuals with chronic pain were recruited in 4 groups (n=30): 1-methadone for opioid addiction; 2-buprenorphine for opioid addiction; 3-history of opioid maintenance treatment for opioid addiction but with prolonged abstinence (M=121 weeks; SD=23.3); and 4-opioid naïve controls. Participants completed a psychological assessment and a cold water task including, time to first pain (sensitivity) and time to stopping the pain task (tolerance). Data analysis used survival analyses. Results A Kaplan-Meier-Cox survival analysis showed group differences for both pain sensitivity (Log rank=15.50; p<.001) and tolerance (Log rank=20.11; p<.001). Current or historical use of opioid maintenance resulted in differing pain sensitivity compared to opioid naïve (p’s<.01). However, tolerance to pain was better among those with a history of opioid maintenance compared to active methadone patients (p<.05), with the highest tolerance found among opioid naïve control group participants (p’s<.001). Correlations within the prolonged abstinent group indicated pain tolerance was significantly improved as length of opioid abstinence increased (R=.37; p<.05); but duration of abstinence did not alter sensitivity (ns). Conclusion Among individuals with a history of prolonged opioid maintenance, there appears to be long-term differences in pain sensitivity that do not resolve with discontinuation of opioid maintenance. Although pain sensitivity does not change, pain tolerance does improve after opioid maintenance cessation. Implications for treating co-morbid opioid addiction and pain (acute and chronic) are discussed. PMID:25456326

Co-morbid pain and opioid addiction: long term effect of opioid maintenance on acute pain.

PubMed

Wachholtz, Amy; Gonzalez, Gerardo

2014-12-01

Medication assisted treatment for opioid dependence alters the pain experience. This study will evaluate changes pain sensitivity and tolerance with opioid treatments; and duration of this effect after treatment cessation. 120 Individuals with chronic pain were recruited in 4 groups (N = 30): 1-methadone for opioid addiction; 2-buprenorphine for opioid addiction; 3-history of opioid maintenance treatment for opioid addiction but with prolonged abstinence (M = 121 weeks; SD = 23.3); and 4-opioid naïve controls. Participants completed a psychological assessment and a cold water task including, time to first pain (sensitivity) and time to stopping the pain task (tolerance). Data analysis used survival analyses. A Kaplan-Meier-Cox survival analysis showed group differences for both pain sensitivity (log rank = 15.50; p < .001) and tolerance (log rank = 20.11; p < .001). Current or historical use of opioid maintenance resulted in differing pain sensitivity compared to opioid naïve (p's < .01). However, tolerance to pain was better among those with a history of opioid maintenance compared to active methadone patients (p < .05), with the highest tolerance found among opioid naïve control group participants (p's < .001). Correlations within the prolonged abstinent group indicated pain tolerance was significantly improved as length of opioid abstinence increased (R = .37; p < .05); but duration of abstinence did not alter sensitivity (ns). Among individuals with a history of prolonged opioid maintenance, there appears to be long-term differences in pain sensitivity that do not resolve with discontinuation of opioid maintenance. Although pain sensitivity does not change, pain tolerance does improve after opioid maintenance cessation. Implications for treating co-morbid opioid addiction and pain (acute and chronic) are discussed. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Hyaluronic acid improves "pleasantness" and tolerability of nebulized hypertonic saline in a cohort of patients with cystic fibrosis.

PubMed

Buonpensiero, Paolo; De Gregorio, Fabiola; Sepe, Angela; Di Pasqua, Antonio; Ferri, Pasqualina; Siano, Maria; Terlizzi, Vito; Raia, Valeria

2010-11-01

Inhaled hypertonic saline improves lung function and decreases pulmonary exacerbations in people with cystic fibrosis. However, side effects such as cough, narrowing of airways and saltiness cause intolerance of the therapy in 8% of patients. The aim of our study was to compare the effect of an inhaled solution of hyaluronic acid and hypertonic saline with hypertonic solution alone on safety and tolerability. A total of 20 patients with cystic fibrosis aged 6 years and over received a single treatment regimen of 7% hypertonic saline solution or hypertonic solution with 0.1% hyaluronate for 2 days nonconsecutively after a washout period in an open crossover study. Cough, throat irritation, and salty taste were evaluated by a modified ordinal score for assessing tolerability; "pleasantness" was evaluated by a five-level, Likert-type scale. Forced expiratory volume in 1 second was registered before and after the end of the saline inhalations. All 20 patients (nine males, 11 females, mean age 13 years, range 8.9-17.7) completed the study. The inhaled solution of 0.1% hyaluronic acid and hypertonic saline significantly improved tolerability and pleasantness compared to hypertonic saline alone. No major adverse effects were observed. No difference was documented in pulmonary function tests between the two treatments. Hyaluronic acid combined with hypertonic saline solution may contribute to improved adherence to hypertonic saline therapy. Further clinical trials are needed to confirm our findings. Considering the extraordinary versatility of hyaluronic acid in biological reactions, perspective studies could define its applicability to halting progression of lung disease in cystic fibrosis.

A rice calcium-dependent protein kinase OsCPK9 positively regulates drought stress tolerance and spikelet fertility

PubMed Central

2014-01-01

Background In plants, calcium-dependent protein kinases (CDPKs) are involved in tolerance to abiotic stresses and in plant seed development. However, the functions of only a few rice CDPKs have been clarified. At present, it is unclear whether CDPKs also play a role in regulating spikelet fertility. Results We cloned and characterized the rice CDPK gene, OsCPK9. OsCPK9 transcription was induced by abscisic acid (ABA), PEG6000, and NaCl treatments. The results of OsCPK9 overexpression (OsCPK9-OX) and OsCPK9 RNA interference (OsCPK9-RNAi) analyses revealed that OsCPK9 plays a positive role in drought stress tolerance and spikelet fertility. Physiological analyses revealed that OsCPK9 improves drought stress tolerance by enhancing stomatal closure and by improving the osmotic adjustment ability of the plant. It also improves pollen viability, thereby increasing spikelet fertility. In OsCPK9-OX plants, shoot and root elongation showed enhanced sensitivity to ABA, compared with that of wild-type. Overexpression and RNA interference of OsCPK9 affected the transcript levels of ABA- and stress-responsive genes. Conclusions Our results demonstrated that OsCPK9 is a positive regulator of abiotic stress tolerance, spikelet fertility, and ABA sensitivity. PMID:24884869

Suppression of a NAC-like transcription factor gene improves boron-toxicity tolerance in rice.

PubMed

Ochiai, Kumiko; Shimizu, Akifumi; Okumoto, Yutaka; Fujiwara, Toru; Matoh, Toru

2011-07-01

We identified a gene responsible for tolerance to boron (B) toxicity in rice (Oryza sativa), named BORON EXCESS TOLERANT1. Using recombinant inbred lines derived from the B-toxicity-sensitive indica-ecotype cultivar IR36 and the tolerant japonica-ecotype cultivar Nekken 1, the region responsible for tolerance to B toxicity was narrowed to 49 kb on chromosome 4. Eight genes are annotated in this region. The DNA sequence in this region was compared between the B-toxicity-sensitive japonica cultivar Wataribune and the B-toxicity-tolerant japonica cultivar Nipponbare by eco-TILLING analysis and revealed a one-base insertion mutation in the open reading frame sequence of the gene Os04g0477300. The gene encodes a NAC (NAM, ATAF, and CUC)-like transcription factor and the function of the transcript is abolished in B-toxicity-tolerant cultivars. Transgenic plants in which the expression of Os04g0477300 is abolished by RNA interference gain tolerance to B toxicity.

Suppression of a NAC-Like Transcription Factor Gene Improves Boron-Toxicity Tolerance in Rice1

PubMed Central

Ochiai, Kumiko; Shimizu, Akifumi; Okumoto, Yutaka; Fujiwara, Toru; Matoh, Toru

2011-01-01

We identified a gene responsible for tolerance to boron (B) toxicity in rice (Oryza sativa), named BORON EXCESS TOLERANT1. Using recombinant inbred lines derived from the B-toxicity-sensitive indica-ecotype cultivar IR36 and the tolerant japonica-ecotype cultivar Nekken 1, the region responsible for tolerance to B toxicity was narrowed to 49 kb on chromosome 4. Eight genes are annotated in this region. The DNA sequence in this region was compared between the B-toxicity-sensitive japonica cultivar Wataribune and the B-toxicity-tolerant japonica cultivar Nipponbare by eco-TILLING analysis and revealed a one-base insertion mutation in the open reading frame sequence of the gene Os04g0477300. The gene encodes a NAC (NAM, ATAF, and CUC)-like transcription factor and the function of the transcript is abolished in B-toxicity-tolerant cultivars. Transgenic plants in which the expression of Os04g0477300 is abolished by RNA interference gain tolerance to B toxicity. PMID:21543724

Improving Saccharomyces cerevisiae ethanol production and tolerance via RNA polymerase II subunit Rpb7.

PubMed

Qiu, Zilong; Jiang, Rongrong

2017-01-01

Classical strain engineering methods often have limitations in altering multigenetic cellular phenotypes. Here we try to improve Saccharomyces cerevisiae ethanol tolerance and productivity by reprogramming its transcription profile through rewiring its key transcription component RNA polymerase II (RNAP II), which plays a central role in synthesizing mRNAs. This is the first report on using directed evolution method to engineer RNAP II to alter S. cerevisiae strain phenotypes. Error-prone PCR was employed to engineer the subunit Rpb7 of RNAP II to improve yeast ethanol tolerance and production. Based on previous studies and the presumption that improved ethanol resistance would lead to enhanced ethanol production, we first isolated variant M1 with much improved resistance towards 8 and 10% ethanol. The ethanol titers of M1 was ~122 g/L (96.58% of the theoretical yield) under laboratory very high gravity (VHG) fermentation, 40% increase as compared to the control. DNA microarray assay showed that 369 genes had differential expression in M1 after 12 h VHG fermentation, which are involved in glycolysis, alcoholic fermentation, oxidative stress response, etc. This is the first study to demonstrate the possibility of engineering eukaryotic RNAP to alter global transcription profile and improve strain phenotypes. Targeting subunit Rpb7 of RNAP II was able to bring differential expression in hundreds of genes in S. cerevisiae , which finally led to improvement in yeast ethanol tolerance and production.

Overexpression of AtEDT1/HDG11 in Chinese Kale (Brassica oleracea var. alboglabra) Enhances Drought and Osmotic Stress Tolerance

PubMed Central

Zhu, Zhangsheng; Sun, Binmei; Xu, Xiaoxia; Chen, Hao; Zou, Lifang; Chen, Guoju; Cao, Bihao; Chen, Changming; Lei, Jianjun

2016-01-01

Plants are constantly challenged by environmental stresses, including drought and high salinity. Improvement of drought and osmotic stress tolerance without yield decrease has been a great challenge in crop improvement. The Arabidopsis ENHANCED DROUGHT TOLERANCE1/HOMEODOMAIN GLABROUS11 (AtEDT1/HDG11), a protein of the class IV HD-Zip family, has been demonstrated to significantly improve drought tolerance in Arabidopsis, rice, and pepper. Here, we report that AtEDT1/HDG11 confers drought and osmotic stress tolerance in the Chinese kale. AtEDT1/HDG11-overexpression lines exhibit auxin-overproduction phenotypes, such as long hypocotyls, tall stems, more root hairs, and a larger root system architecture. Compared with the untransformed control, transgenic lines have significantly reduced stomatal density. In the leaves of transgenic Chinese kale plants, proline (Pro) content and reactive oxygen species-scavenging enzyme activity was significantly increased after drought and osmotic stress, particularly compared to wild kale. More importantly, AtEDT1/HDG11-overexpression leads to abscisic acid (ABA) hypersensitivity, resulting in ABA inhibitor germination and induced stomatal closure. Consistent with observed phenotypes, the expression levels of auxin, ABA, and stress-related genes were also altered under both normal and/or stress conditions. Further analysis showed that AtEDT1/HDG11, as a transcription factor, can target the auxin biosynthesis gene YUCC6 and ABA response genes ABI3 and ABI5. Collectively, our results provide a new insight into the role of AtEDT1/HDG11 in enhancing abiotic stress resistance through auxin- and ABA-mediated signaling response in Chinese kale. PMID:27625663

Overexpression of AtEDT1/HDG11 in Chinese Kale (Brassica oleracea var. alboglabra) Enhances Drought and Osmotic Stress Tolerance.

PubMed

Zhu, Zhangsheng; Sun, Binmei; Xu, Xiaoxia; Chen, Hao; Zou, Lifang; Chen, Guoju; Cao, Bihao; Chen, Changming; Lei, Jianjun

2016-01-01

Plants are constantly challenged by environmental stresses, including drought and high salinity. Improvement of drought and osmotic stress tolerance without yield decrease has been a great challenge in crop improvement. The Arabidopsis ENHANCED DROUGHT TOLERANCE1/HOMEODOMAIN GLABROUS11 (AtEDT1/HDG11), a protein of the class IV HD-Zip family, has been demonstrated to significantly improve drought tolerance in Arabidopsis, rice, and pepper. Here, we report that AtEDT1/HDG11 confers drought and osmotic stress tolerance in the Chinese kale. AtEDT1/HDG11-overexpression lines exhibit auxin-overproduction phenotypes, such as long hypocotyls, tall stems, more root hairs, and a larger root system architecture. Compared with the untransformed control, transgenic lines have significantly reduced stomatal density. In the leaves of transgenic Chinese kale plants, proline (Pro) content and reactive oxygen species-scavenging enzyme activity was significantly increased after drought and osmotic stress, particularly compared to wild kale. More importantly, AtEDT1/HDG11-overexpression leads to abscisic acid (ABA) hypersensitivity, resulting in ABA inhibitor germination and induced stomatal closure. Consistent with observed phenotypes, the expression levels of auxin, ABA, and stress-related genes were also altered under both normal and/or stress conditions. Further analysis showed that AtEDT1/HDG11, as a transcription factor, can target the auxin biosynthesis gene YUCC6 and ABA response genes ABI3 and ABI5. Collectively, our results provide a new insight into the role of AtEDT1/HDG11 in enhancing abiotic stress resistance through auxin- and ABA-mediated signaling response in Chinese kale.

Screening of Non- Saccharomyces cerevisiae Strains for Tolerance to Formic Acid in Bioethanol Fermentation.

PubMed

Oshoma, Cyprian E; Greetham, Darren; Louis, Edward J; Smart, Katherine A; Phister, Trevor G; Powell, Chris; Du, Chenyu

2015-01-01

Formic acid is one of the major inhibitory compounds present in hydrolysates derived from lignocellulosic materials, the presence of which can significantly hamper the efficiency of converting available sugars into bioethanol. This study investigated the potential for screening formic acid tolerance in non-Saccharomyces cerevisiae yeast strains, which could be used for the development of advanced generation bioethanol processes. Spot plate and phenotypic microarray methods were used to screen the formic acid tolerance of 7 non-Saccharomyces cerevisiae yeasts. S. kudriavzeii IFO1802 and S. arboricolus 2.3319 displayed a higher formic acid tolerance when compared to other strains in the study. Strain S. arboricolus 2.3319 was selected for further investigation due to its genetic variability among the Saccharomyces species as related to Saccharomyces cerevisiae and availability of two sibling strains: S. arboricolus 2.3317 and 2.3318 in the lab. The tolerance of S. arboricolus strains (2.3317, 2.3318 and 2.3319) to formic acid was further investigated by lab-scale fermentation analysis, and compared with S. cerevisiae NCYC2592. S. arboricolus 2.3319 demonstrated improved formic acid tolerance and a similar bioethanol synthesis capacity to S. cerevisiae NCYC2592, while S. arboricolus 2.3317 and 2.3318 exhibited an overall inferior performance. Metabolite analysis indicated that S. arboricolus strain 2.3319 accumulated comparatively high concentrations of glycerol and glycogen, which may have contributed to its ability to tolerate high levels of formic acid.

Screening of Non- Saccharomyces cerevisiae Strains for Tolerance to Formic Acid in Bioethanol Fermentation

PubMed Central

Oshoma, Cyprian E.; Greetham, Darren; Louis, Edward J.; Smart, Katherine A.; Phister, Trevor G.; Powell, Chris; Du, Chenyu

2015-01-01

Formic acid is one of the major inhibitory compounds present in hydrolysates derived from lignocellulosic materials, the presence of which can significantly hamper the efficiency of converting available sugars into bioethanol. This study investigated the potential for screening formic acid tolerance in non-Saccharomyces cerevisiae yeast strains, which could be used for the development of advanced generation bioethanol processes. Spot plate and phenotypic microarray methods were used to screen the formic acid tolerance of 7 non-Saccharomyces cerevisiae yeasts. S. kudriavzeii IFO1802 and S. arboricolus 2.3319 displayed a higher formic acid tolerance when compared to other strains in the study. Strain S. arboricolus 2.3319 was selected for further investigation due to its genetic variability among the Saccharomyces species as related to Saccharomyces cerevisiae and availability of two sibling strains: S. arboricolus 2.3317 and 2.3318 in the lab. The tolerance of S. arboricolus strains (2.3317, 2.3318 and 2.3319) to formic acid was further investigated by lab-scale fermentation analysis, and compared with S. cerevisiae NCYC2592. S. arboricolus 2.3319 demonstrated improved formic acid tolerance and a similar bioethanol synthesis capacity to S. cerevisiae NCYC2592, while S. arboricolus 2.3317 and 2.3318 exhibited an overall inferior performance. Metabolite analysis indicated that S. arboricolus strain 2.3319 accumulated comparatively high concentrations of glycerol and glycogen, which may have contributed to its ability to tolerate high levels of formic acid. PMID:26284784

Improving the Fatigue Crack Propagation Resistance and Damage Tolerance of 2524-T3 Alloy with Amorphous Electroless Ni-P Coating

NASA Astrophysics Data System (ADS)

Chen, Lai; Zeng, Diping; Liu, Zhiyi; Bai, Song; Li, Junlin

2018-02-01

The surface microhardness, as well as the fatigue crack propagation (FCP) resistance of 2524-T3 alloy, is improved by producing a 20-μm-thick amorphous electroless Ni-12% P coating on its surface. Compared to the substrate, this deposited EN coating possesses higher strength properties and exhibits a greater ability of accommodating the plastic deformation at the fatigue crack tip, thereby remarkably improving the FCP resistance in near-threshold and early Paris regimes. Regardless of the similar FCP rates in Paris regime (Δ K ≥ 16.2 MPa m0.5), the coated sample exhibits extended Paris regime and enhanced damage tolerance.

Frost trends and their estimated impact on yield in the Australian wheatbelt

PubMed Central

Zheng, Bangyou; Chapman, Scott C.; Christopher, Jack T.; Frederiks, Troy M.; Chenu, Karine

2015-01-01

Radiant spring frosts occurring during reproductive developmental stages can result in catastrophic yield loss for wheat producers. To better understand the spatial and temporal variability of frost, the occurrence and impact of frost events on rain-fed wheat production was estimated across the Australian wheatbelt for 1957–2013 using a 0.05 ° gridded weather data set. Simulated yield outcomes at 60 key locations were compared with those for virtual genotypes with different levels of frost tolerance. Over the last six decades, more frost events, later last frost day, and a significant increase in frost impact on yield were found in certain regions of the Australian wheatbelt, in particular in the South-East and West. Increasing trends in frost-related yield losses were simulated in regions where no significant trend of frost occurrence was observed, due to higher mean temperatures accelerating crop development and causing sensitive post-heading stages to occur earlier, during the frost risk period. Simulations indicated that with frost-tolerant lines the mean national yield could be improved by up to 20% through (i) reduced frost damage (~10% improvement) and (ii) the ability to use earlier sowing dates (adding a further 10% improvement). In the simulations, genotypes with an improved frost tolerance to temperatures 1 °C lower than the current 0 °C reference provided substantial benefit in most cropping regions, while greater tolerance (to 3 °C lower temperatures) brought further benefits in the East. The results indicate that breeding for improved reproductive frost tolerance should remain a priority for the Australian wheat industry, despite warming climates. PMID:25922479

The total face mask is more comfortable than the oronasal mask in noninvasive ventilation but is not associated with improved outcome.

PubMed

Chacur, Fernando Hauaji; Vilella Felipe, Luis Marcelo; Fernandes, Cintia Gonçalves; Lazzarini, Luiz Claudio Oliveira

2011-01-01

Noninvasive positive-pressure ventilation (NPPV) is commonly used to improve ventilation and oxygenation and avoid endotracheal intubation and mechanical ventilation. Although clinically indicated, most patients fail to use NPPV due to mask intolerance. A total face mask was designed to increase compliance, but whether this translates into better outcome (improvement in clinical and blood gas parameters and less intubation) is unknown. We compared the evolution of the clinical parameters, blood gases, levels of ventilatory support and rate of endotracheal intubation using the total face mask or the traditional oronasal mask during NPPV. A total of 60 patients were randomized to use either mask during NPPV. The clinical and laboratory parameters, as well as the level of ventilatory support were recorded at different intervals in both groups for up to 6 h. In addition, the tolerance for each mask and the need for endotracheal intubation were compared. Patients tolerated the total face mask significantly better (p = 0.0010) and used NPPV for a longer time (p = 0.0017) when compared with the oronasal mask. Just 1 patient switched to the total face mask because of intolerance. Although better tolerated, the rate of endotracheal intubation was similar in both groups (p = 0.4376), as was the clinical and laboratory evolution. The total face mask was more comfortable, allowing the patients to tolerate NPPV longer; however, these accomplishments did not translate into a better outcome. Due to its comfort, the total face mask should be available, at least as an option, in units where NPPVs are routinely applied. Copyright © 2011 S. Karger AG, Basel.

Acetone, butanol, and ethanol production from gelatinized cassava flour by a new isolates with high butanol tolerance.

PubMed

Li, Han-Guang; Ofosu, Fred Kwame; Li, Kun-Tai; Gu, Qiu-Ya; Wang, Qiang; Yu, Xiao-Bin

2014-11-01

To obtain native strains resistant to butanol toxicity, a new isolating method and serial enrichment was used in this study. With this effort, mutant strain SE36 was obtained, which could withstand 35g/L (compared to 20g/L of the wild-type strain) butanol challenge. Based on 16s rDNA comparison, the mutant strain was identified as Clostridium acetobutylicum. Under the optimized condition, the phase shift was smoothly triggered and fermentation performances were consequently enhanced. The maximum total solvent and butanol concentration were 23.6% and 24.3%, respectively higher than that of the wild-type strain. Furthermore, the correlation between butanol produced and the butanol tolerance was investigated, suggesting that enhancing butanol tolerance could improve butanol production. These results indicate that the simple but effective isolation method and acclimatization process are a promising technique for isolation and improvement of butanol tolerance and production. Copyright © 2014 Elsevier Ltd. All rights reserved.

Vildagliptin: a new oral treatment for type 2 diabetes mellitus

PubMed Central

Mathieu, Chantal; Degrande, Evy

2008-01-01

Vildagliptin is a new oral antidiabetic agent that enhances pancreatic islet cell responsiveness to glucose. An extensive clinical program involving approximately 22,000 patients and 7000 patient-years of exposure to vildagliptin has shown that the agent is well tolerated and efficacious in improving glycemic control in patients with type 2 diabetes mellitus (T2DM). Monotherapy trials have shown that significant HbA1c lowering is accompanied by body weight-neutral and lipid-neutral effects, low risk of edema, and low risk of hypoglycemia. These characteristics make vildagliptin a favorable partner for combination therapy. Studies of vildagliptin as an add-on to metformin have shown significant improvements in glycemic control (comparable to that of thiazolidinedione add-on), with the combination being well tolerated and associated with low risks for hypoglycemia and adverse effects on weight or lipid levels. Good tolerability and clinically relevant improvements in glycemic control have also been observed with vildagliptin as an add-on treatment to sulfonylurea, thiazolidinedione, or insulin treatment or in initial combination treatment with pioglitazone. Improved β-cell function and glycemic control have been shown with vildagliptin in subjects with impaired glucose tolerance and in T2DM patients with mild hyperglycemia, with some evidence in the latter suggesting the potential for modifying disease course. PMID:19337548

Improved catalytic efficiency, thermophilicity, anti-salt and detergent tolerance of keratinase KerSMD by partially truncation of PPC domain

PubMed Central

Fang, Zhen; Zhang, Juan; Du, Guocheng; Chen, Jian

2016-01-01

The keratinase from Stenotrophomonas maltophilia (KerSMD) is known for its high activity and pH stability in keratin degradation. However, catalytic efficiency and detergent tolerability need to be improved in order to be used for industrial application. In this work, we obtained several keratinase variants with enhanced catalytic efficiency, thermophilicity, and anti-salt and detergent tolerability by partially truncating the PPC domain of KerSMD. The variants all showed improved catalytic efficiency to synthetic substrate AAPF, with the V355 variant having the highest kcat /Km value of 143.6 s−1 mM−1. The truncation of keratinase had little effect on alkaline stability but obviously decreased collagenase activity, developing its potential application in leather treatment. The variants V380, V370, and V355 were thermophilic, with a 1.7-fold enhancement of keratinlytic activity at 60 °C when compared to the wild type. The entire truncation of PPC domain obtained the variant V355 with improved tolerance to alkalinity, salt, chaotropic agents, and detergents. The V355 variant showed more than a 40% improvement in activity under 15% (w/v) NaCl or 4% (w/v) SDS solution, showing excellent stability under harsh washing and unhairing conditions. Our work investigated how protein engineering affects the function of PPC domain of KerSMD. PMID:27298079

Improved catalytic efficiency, thermophilicity, anti-salt and detergent tolerance of keratinase KerSMD by partially truncation of PPC domain.

PubMed

Fang, Zhen; Zhang, Juan; Du, Guocheng; Chen, Jian

2016-06-14

The keratinase from Stenotrophomonas maltophilia (KerSMD) is known for its high activity and pH stability in keratin degradation. However, catalytic efficiency and detergent tolerability need to be improved in order to be used for industrial application. In this work, we obtained several keratinase variants with enhanced catalytic efficiency, thermophilicity, and anti-salt and detergent tolerability by partially truncating the PPC domain of KerSMD. The variants all showed improved catalytic efficiency to synthetic substrate AAPF, with the V355 variant having the highest kcat /Km value of 143.6 s(-1) mM(-1). The truncation of keratinase had little effect on alkaline stability but obviously decreased collagenase activity, developing its potential application in leather treatment. The variants V380, V370, and V355 were thermophilic, with a 1.7-fold enhancement of keratinlytic activity at 60 °C when compared to the wild type. The entire truncation of PPC domain obtained the variant V355 with improved tolerance to alkalinity, salt, chaotropic agents, and detergents. The V355 variant showed more than a 40% improvement in activity under 15% (w/v) NaCl or 4% (w/v) SDS solution, showing excellent stability under harsh washing and unhairing conditions. Our work investigated how protein engineering affects the function of PPC domain of KerSMD.

Bile salt tolerance of Lactococcus lactis is enhanced by expression of bile salt hydrolase thereby producing less bile acid in the cells.

PubMed

Bi, Jie; Liu, Song; Du, Guocheng; Chen, Jian

2016-04-01

Changes of bile salt tolerance, morphology and amount of bile acid within cells were studied to evaluate the exact effects of bile salt hydrolase (BSH) on bile salt tolerance of microorganism. The effect of BSHs on the bile salt tolerance of Lactococcus lactis was examined by expressing two BSHs (BSH1 and BSH2). Growth of L. lactis expressing BSH1 or BSH2 was better under bile salt stress compared to wild-type L. lactis. As indicated by transmission electron microscopy, bile acids released by the action of BSH induced the formation of micelles around the membrane surface of cells subject to conjugated bile salt stress. A similar micelle containing bile acid was observed in the cytoplasm by liquid chromatography-mass spectrometry. BSH1 produced fewer bile acid micelles in the cytoplasm and achieved better cell growth of L. lactis compared to BSH2. Expression of BSH improved bile salt tolerance of L. lactis but excessive production by BSH of bile acid micelles in the cytoplasm inhibited cell growth.

Fasting Serum Taurine-Conjugated Bile Acids Are Elevated in Type 2 Diabetes and Do Not Change With Intensification of Insulin

PubMed Central

Wewalka, Marlene; Patti, Mary-Elizabeth; Barbato, Corinne; Houten, Sander M.

2014-01-01

Context: Bile acids (BAs) are newly recognized signaling molecules in glucose and energy homeostasis. Differences in BA profiles with type 2 diabetes mellitus (T2D) remain incompletely understood. Objective: The objective of the study was to assess serum BA composition in impaired glucose-tolerant, T2D, and normal glucose-tolerant persons and to monitor the effects of improving glycemia on serum BA composition in T2D patients. Design and Setting: This was a cross-sectional cohort study in a general population (cohort 1) and nonrandomized intervention (cohort 2). Patients and Interventions: Ninety-nine volunteers underwent oral glucose tolerance testing, and 12 persons with T2D and hyperglycemia underwent 8 weeks of intensification of treatment. Main Outcome Measures: Serum free BA and respective taurine and glycine conjugates were measured by HPLC tandem mass spectrometry. Results: Oral glucose tolerance testing identified 62 normal-, 25 impaired glucose-tolerant, and 12 T2D persons. Concentrations of total taurine-conjugated BA were higher in T2D and intermediate in impaired- compared with normal glucose-tolerant persons (P = .009). Univariate regression revealed a positive association between total taurine-BA and fasting glucose (R = 0.37, P < .001), postload glucose (R = 0.31, P < .002), hemoglobin A1c (R = 0.26, P < .001), fasting insulin (R = 0.21, P = .03), and homeostatic model assessment-estimated insulin resistance (R = 0.26, P = .01) and an inverse association with oral disposition index (R = −0.36, P < .001). Insulin-mediated glycemic improvement in T2D patients did not change fasting serum total BA or BA composition. Conclusion: Fasting taurine-conjugated BA concentrations are higher in T2D and intermediate in impaired compared with normal glucose-tolerant persons and are associated with fasting and postload glucose. Serum BAs are not altered in T2D in response to improved glycemia. Further study may elucidate whether this pattern of taurine-BA conjugation can be targeted to provide novel therapeutic approaches to treat T2D. PMID:24432996

A somatostatin analog improves tilt table tolerance by decreasing splanchnic vascular conductance

PubMed Central

Florian, J. P.; Curren, M. J.; Pawelczyk, J. A.

2012-01-01

Splanchnic hemodynamics and tilt table tolerance were assessed after an infusion of placebo or octreotide acetate, a somatostatin analog whose vascular effects are largely confined to the splanchnic circulation. We hypothesized that reductions in splanchnic blood flow (SpBF) and splanchnic vascular conductance (SpVC) would be related to improvements in tilt table tolerance. In randomized, double-blind, crossover trials, hemodynamic variables were collected in 14 women and 16 men during baseline, 70° head-up tilt (HUT), and recovery. A repeated-measures analysis of variance was used to compare changes from baseline with respect to sex and condition. HUT elicited an increase in heart rate and decreases in mean arterial pressure, cardiac index, stroke index, and systemic vascular conductance. Additionally, SpVC and non-SpVC were lower during HUT. Octreotide reduced SpBF and SpVC and increased systemic vascular conductance and non-SpVC. Changes in SpBF and SpVC between supine and HUT were smaller in women (P < 0.05). Tilt table tolerance was increased after administration of octreotide [median tilt time: 15.7 vs. 37.0 min (P < 0.05) and 21.8 vs. 45.0 min (P < 0.05) for women and men, respectively]. A significant relationship existed between change (Δ) in SpBF (placebo-octreotide) and Δtilt time in women (Δtilt time = 2.5–0.0083 ΔSpBF, P < 0.01), but not men (Δtilt time = 3.41–0.0008 ΔSpBF, P = 0.59). In conclusion, administration of octreotide acetate improved tilt table tolerance, which was associated with a decrease in SpVC. In women, but not men, the magnitude of reduction in SpBF was positively associated with improvements in tilt tolerance. PMID:22345429

Shaped fiber composites

DOEpatents

Kinnan, Mark K.; Roach, Dennis P.

2017-12-05

A composite article is disclosed that has non-circular fibers embedded in a polymer matrix. The composite article has improved damage tolerance, toughness, bending, and impact resistance compared to composites having traditional round fibers.

Impact of pseudo-continuous fermentation on the ethanol tolerance of Scheffersomyces stipitis.

PubMed

Liang, Meng; Kim, Min Hea; He, Qinghua Peter; Wang, Jin

2013-09-01

In this work we conducted the pseudo-continuous fermentation, i.e., continuous fermentation with cell retention, using Scheffersomyces stipitis, and studied its effect on ethanol tolerance of the strain. During the fermentation experiments, S. stipitis was adapted to a mild concentration of ethanol (20-26 g/L) for two weeks. Two substrates (glucose and xylose) were used in different fermentation experiments. After fermentation, various experiments were performed to evaluate the ethanol tolerance of adapted cells and unadapted cells. Compared to the unadapted cells, the viability of adapted cells increased by 8 folds with glucose as the carbon source and 6 folds with xylose as the carbon source following exposure to 60 g/L ethanol for 2 h. Improved ethanol tolerance of the adapted cells was also revealed in the effects of ethanol on plasma membrane permeability, extracellular alkalization and acidification. The mathematical modeling of cell leakage, extracellular alkalization and acidification revealed that cells cultured on glucose show better ethanol tolerance than cells cultured on xylose but the differences become smaller for adapted cells. The results show that pseudo-continuous fermentation can effectively improve cell's ethanol tolerance due to the environmental pressure during the fermentation process. Copyright © 2013 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Efficacy, safety, and improved tolerability of travoprost BAK-free ophthalmic solution compared with prior prostaglandin therapy

PubMed Central

Henry, J Charles; Peace, James H; Stewart, Jeanette A; Stewart, William C

2008-01-01

Purpose To evaluate the efficacy, safety and tolerability of changing to travoprost BAK-free from prior prostaglandin therapy in patients with primary open-angle glaucoma or ocular hypertension. Design Prospective, multi-center, historical control study. Methods Patients treated with latanoprost or bimatoprost who needed alternative therapy due to tolerability issues were enrolled. Patients were surveyed using the Ocular Surface Disease Index (OSDI) to evaluate OSD symptoms prior to changing to travoprost BAK-free dosed once every evening. Patients were re-evaluated 3 months later. Results In 691 patients, travoprost BAK-free demonstrated improved mean OSDI scores compared to either latanoprost or bimatoprost (p < 0.0001). Patients having any baseline OSD symptoms (n = 235) demonstrated significant improvement after switching to travoprost BAK-free (p < 0.0001). In 70.2% of these patients, symptoms were reduced in severity by at least 1 level. After changing medications to travoprost BAK-free, mean intraocular pressure (IOP) was significantly decreased (p < 0.0001). Overall, 72.4% preferred travoprost BAK-free (p < 0.0001, travoprost BAK-free vs prior therapy). Travoprost BAK-free demonstrated less conjunctival hyperemia than either prior therapy (p < 0.0001). Conclusions Patients previously treated with a BAK-preserved prostaglandin analog who are changed to travoprost BAK-free have clinically and statistically significant improvement in their OSD symptoms, decreased hyperemia, and equal or better IOP control. PMID:19668762

Soybean Salt Tolerance 1 (GmST1) Reduces ROS Production, Enhances ABA Sensitivity, and Abiotic Stress Tolerance in Arabidopsis thaliana.

PubMed

Ren, Shuxin; Lyle, Chimera; Jiang, Guo-Liang; Penumala, Abhishek

2016-01-01

Abiotic stresses, including high soil salinity, significantly reduce crop production worldwide. Salt tolerance in plants is a complex trait and is regulated by multiple mechanisms. Understanding the mechanisms and dissecting the components on their regulatory pathways will provide new insights, leading to novel strategies for the improvement of salt tolerance in agricultural and economic crops of importance. Here we report that soybean salt tolerance 1, named GmST1, exhibited strong tolerance to salt stress in the Arabidopsis transgenic lines. The GmST1-overexpressed Arabidopsis also increased sensitivity to ABA and decreased production of reactive oxygen species under salt stress. In addition, GmST1 significantly improved drought tolerance in Arabidopsis transgenic lines. GmST1 belongs to a 3-prime part of Glyma.03g171600 gene in the current version of soybean genome sequence annotation. However, comparative reverse transcription-polymerase chain reaction analysis around Glyma.03g171600 genomic region confirmed that GmST1 might serve as an intact gene in soybean leaf tissues. Unlike Glyma.03g171600 which was not expressed in leaves, GmST1 was strongly induced by salt treatment in the leaf tissues. By promoter analysis, a TATA box was detected to be positioned close to GmST1 start codon and a putative ABRE and a DRE cis-acting elements were identified at about 1 kb upstream of GmST1 gene. The data also indicated that GmST1-transgenic lines survived under drought stress and showed a significantly lower water loss than non-transgenic lines. In summary, our results suggest that overexpression of GmST1 significantly improves Arabidopsis tolerance to both salt and drought stresses and the gene may be a potential candidate for genetic engineering of salt- and drought-tolerant crops.

Real-life feasibility and effectiveness of home-based pulmonary rehabilitation in chronic obstructive pulmonary disease requiring medical equipment.

PubMed

Coquart, Jérémy B; Le Rouzic, Olivier; Racil, Ghazi; Wallaert, Benoit; Grosbois, Jean-Marie

2017-01-01

Pulmonary rehabilitation (PR) is a key treatment of chronic obstructive pulmonary disease (COPD) but studies are still needed to identify the most pertinent criteria to personalize this intervention and improve its efficacy. This real-life retrospective study compared the effects of home-based PR on exercise tolerance, anxiety, depression, and health-related quality of life (HRQoL) in COPD patients, according to their medical equipment. Exercise tolerance, anxiety, depression, and HRQoL were evaluated in 109 patients equipped with long-term oxygen therapy (LTOT), 84 patients with noninvasive ventilation (NIV), 25 patients with continuous positive airway pressure (CPAP), and 80 patients with no equipment (NE), before, just after, and 6 and 12 months after PR. At baseline, the body mass index in the CPAP and NIV groups was higher ( p <0.05) than in the other two groups, and the forced expiratory volume in 1 second was lower in the LTOT and NIV groups ( p <0.001). All parameters improved after PR in the four groups ( p <0.05), but for exercise tolerance, only the 6-minute stepper test showed maintained improvement after 6 and 12 months, whereas the 10 times sit-to-stand and timed up-and-go tests were only improved just after PR. At every time point, exercise tolerance was lower in the LTOT group ( p <0.05), with a similar trend in the NIV group. Despite differences in the medical equipment to treat COPD, home-based PR showed comparable feasibility, safety, and efficacy in all equipment-based groups. Medical equipment should therefore not be a barrier to home-based PR.

High intensity interval exercise is an effective alternative to moderate intensity exercise for improving glucose tolerance and insulin sensitivity in adolescent boys.

PubMed

Cockcroft, Emma J; Williams, Craig A; Tomlinson, Owen W; Vlachopoulos, Dimitris; Jackman, Sarah R; Armstrong, Neil; Barker, Alan R

2015-11-01

High-intensity interval exercise (HIIE) may offer a time efficient means to improve health outcomes compared to moderate-intensity exercise (MIE). This study examined the acute effect of HIIE compared to a work-matched bout of MIE on glucose tolerance, insulin sensitivity (IS), resting fat oxidation and exercise enjoyment in adolescent boys. Within-measures design with counterbalanced experimental conditions. Nine boys (14.2 ± 0.4 years) completed three conditions on separate days in a counterbalanced order: (1) HIIE; (2) work matched MIE, both on a cycle ergometer; and (3) rest (CON). An oral glucose tolerance test (OGTT) was performed after exercise or rest and the area under curve (AUC) responses for plasma [glucose] and [insulin] were calculated, and IS estimated (Cederholm index). Energy expenditure and fat oxidation were measured following the OGTT using indirect calorimetry. Exercise enjoyment was assessed using the Physical Activity Enjoyment Scale. The incremental AUC (iAUC) for plasma [glucose] was reduced following both MIE (-23.9%, P = 0.013, effect size [ES] = -0.64) and HIIE (-28.9%, P=0.008, ES = -0.84) compared to CON. The iAUC for plasma [insulin] was lower for HIIE (-24.2%, P = 0.021, ES = -0.71) and MIE (-29.1%, P = 0.012, ES = -0.79) compared to CON. IS increased by 11.2% after HIIE (P = 0.03, ES = 0.76) and 8.4% after MIE (P = 0.10, ES = 0.58). There was a trend for an increase in fat oxidation following HIIE (P = 0.097, ES = 0.70). Both HIIE and MIE were rated as equally enjoyable (P > 0.05, ES < 0.01). A single bout of time efficient HIIE is an effective alternative to MIE for improving glucose tolerance and IS in adolescent boys immediately after exercise. Copyright © 2014 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Improving glucose tolerance by muscle-damaging exercise.

PubMed

Ho, Chien-Te; Otaka, Machiko; Kuo, Chia-Hua

2017-04-01

Tissue damage is regarded as an unwanted medical condition to be avoided. However, introducing tolerable tissue damages has been used as a therapeutic intervention in traditional and complementary medicine to cure discomfort and illness. Eccentric exercise is known to cause significant necrosis and insulin resistance of skeletal muscle. The purpose of this study was to determine the magnitude of muscle damage and blood glucose responses during an oral glucose tolerance test (OGTT) after eccentric training in 21 young participants. They were challenged by 5 times of 100-meter downhill sprinting and 20 times of squats training at 30 pounds weight load for 3 days, which resulted in a wide spectrum of muscle creatine kinase (CK) surges in plasma, 48 h after the last bout of exercise. Participants were then divided into two groups according the magnitude of CK increases (low CK: +48% ± 0.3; high CK: +137% ± 0.5, P < 0.05). Both groups show comparable decreases in blood glucose levels in OGTT, suggesting that this muscle-damaging exercise does not appear to decrease but rather improve glycemic control in men. The result of the study rejects the hypothesis that eccentric exercise decreases glucose tolerance. Improved glucose tolerance with CK increase implicates a beneficial effect of replacing metabolically weaker muscle fibers by eccentric exercise in Darwinian natural selection fashion.

The Symbiotic Performance of Chickpea Rhizobia Can Be Improved by Additional Copies of the clpB Chaperone Gene.

PubMed

Paço, Ana; Brígido, Clarisse; Alexandre, Ana; Mateos, Pedro F; Oliveira, Solange

2016-01-01

The ClpB chaperone is known to be involved in bacterial stress response. Moreover, recent studies suggest that this protein has also a role in the chickpea-rhizobia symbiosis. In order to improve both stress tolerance and symbiotic performance of a chickpea microsymbiont, the Mesorhizobium mediterraneum UPM-Ca36T strain was genetically transformed with pPHU231 containing an extra-copy of the clpB gene. To investigate if the clpB-transformed strain displays an improved stress tolerance, bacterial growth was evaluated under heat and acid stress conditions. In addition, the effect of the extra-copies of the clpB gene in the symbiotic performance was evaluated using plant growth assays (hydroponic and pot trials). The clpB-transformed strain is more tolerant to heat shock than the strain transformed with pPHU231, supporting the involvement of ClpB in rhizobia heat shock tolerance. Both plant growth assays showed that ClpB has an important role in chickpea-rhizobia symbiosis. The nodulation kinetics analysis showed a higher rate of nodule appearance with the clpB-transformed strain. This strain also induced a greater number of nodules and, more notably, its symbiotic effectiveness increased ~60% at pH5 and 83% at pH7, compared to the wild-type strain. Furthermore, a higher frequency of root hair curling was also observed in plants inoculated with the clpB-transformed strain, compared to the wild-type strain. The superior root hair curling induction, nodulation ability and symbiotic effectiveness of the clpB-transformed strain may be explained by an increased expression of symbiosis genes. Indeed, higher transcript levels of the nodulation genes nodA and nodC (~3 folds) were detected in the clpB-transformed strain. The improvement of rhizobia by addition of extra-copies of the clpB gene may be a promising strategy to obtain strains with enhanced stress tolerance and symbiotic effectiveness, thus contributing to their success as crop inoculants, particularly under environmental stresses. This is the first report on the successful improvement of a rhizobium with a chaperone gene.

The Symbiotic Performance of Chickpea Rhizobia Can Be Improved by Additional Copies of the clpB Chaperone Gene

PubMed Central

Paço, Ana; Brígido, Clarisse; Alexandre, Ana; Mateos, Pedro F.; Oliveira, Solange

2016-01-01

The ClpB chaperone is known to be involved in bacterial stress response. Moreover, recent studies suggest that this protein has also a role in the chickpea-rhizobia symbiosis. In order to improve both stress tolerance and symbiotic performance of a chickpea microsymbiont, the Mesorhizobium mediterraneum UPM-Ca36T strain was genetically transformed with pPHU231 containing an extra-copy of the clpB gene. To investigate if the clpB-transformed strain displays an improved stress tolerance, bacterial growth was evaluated under heat and acid stress conditions. In addition, the effect of the extra-copies of the clpB gene in the symbiotic performance was evaluated using plant growth assays (hydroponic and pot trials). The clpB-transformed strain is more tolerant to heat shock than the strain transformed with pPHU231, supporting the involvement of ClpB in rhizobia heat shock tolerance. Both plant growth assays showed that ClpB has an important role in chickpea-rhizobia symbiosis. The nodulation kinetics analysis showed a higher rate of nodule appearance with the clpB-transformed strain. This strain also induced a greater number of nodules and, more notably, its symbiotic effectiveness increased ~60% at pH5 and 83% at pH7, compared to the wild-type strain. Furthermore, a higher frequency of root hair curling was also observed in plants inoculated with the clpB-transformed strain, compared to the wild-type strain. The superior root hair curling induction, nodulation ability and symbiotic effectiveness of the clpB-transformed strain may be explained by an increased expression of symbiosis genes. Indeed, higher transcript levels of the nodulation genes nodA and nodC (~3 folds) were detected in the clpB-transformed strain. The improvement of rhizobia by addition of extra-copies of the clpB gene may be a promising strategy to obtain strains with enhanced stress tolerance and symbiotic effectiveness, thus contributing to their success as crop inoculants, particularly under environmental stresses. This is the first report on the successful improvement of a rhizobium with a chaperone gene. PMID:26845770

PpCBF3 from Cold-Tolerant Kentucky Bluegrass Involved in Freezing Tolerance Associated with Up-Regulation of Cold-Related Genes in Transgenic Arabidopsis thaliana

PubMed Central

Chen, Yu; Xu, Bin; Yang, Zhimin; Huang, Bingru

2015-01-01

Dehydration-Responsive Element Binding proteins (DREB)/C-repeat (CRT) Binding Factors (CBF) have been identified as transcriptional activators during plant responses to cold stress. The objective of this study was to determine the physiological roles of a CBF gene isolated from a cold-tolerant perennial grass species, Kentucky bluegrass (Poa pratensis L.), which designated as PpCBF3, in regulating plant tolerance to freezing stress. Transient transformation of Arabidopsis thaliana mesophyll protoplast with PpCBF3-eGFP fused protein showed that PpCBF3 was localized to the nucleus. RT-PCR analysis showed that PpCBF3 was specifically induced by cold stress (4°C) but not by drought stress [induced by 20% polyethylene glycol 6000 solution (PEG-6000)] or salt stress (150 mM NaCl). Transgenic Arabidopsis overexpressing PpCBF3 showed significant improvement in freezing (-20°C) tolerance demonstrated by a lower percentage of chlorotic leaves, lower cellular electrolyte leakage (EL) and H2O2 and O2 .- content, and higher chlorophyll content and photochemical efficiency compared to the wild type. Relative mRNA expression level analysis by qRT-PCR indicated that the improved freezing tolerance of transgenic Arabidopsis plants overexpressing PpCBF3 was conferred by sustained activation of downstream cold responsive (COR) genes. Other interesting phenotypic changes in the PpCBF3-transgenic Arabidopsis plants included late flowering and slow growth or ‘dwarfism’, both of which are desirable phenotypic traits for perennial turfgrasses. Therefore, PpCBF3 has potential to be used in genetic engineering for improvement of turfgrass freezing tolerance and other desirable traits. PMID:26177510

The Tolerability Profile of Clindamycin 1%/Benzoyl Peroxide 5% Gel vs. Adapalene 0.1%/Benzoyl Peroxide 2.5% Gel for Facial Acne

PubMed Central

Cirigliano, Marcela; Gwazdauskas, Jennifer A; Gonzalez, Pablo

2012-01-01

Objective: To compare the first two weeks of tolerability of clindamycin/benzoyl peroxide gel versus adapalene/benzoyl peroxide gel followed by six weeks of open-label clindamycin/benzoyl peroxide gel therapy in subjects with mild-to-moderate acne who participated in two eight-week, identically designed, clinical studies. Methods: Using a split-face method, patients received both clindamycin/benzoyl peroxide gel and adapalene/benzoyl peroxide gel once daily for two weeks (allocation to the right or left side of the face was randomized) in an investigator-blinded fashion. Patients then went on to receive a further six weeks of open-label, full-face clindamycin/benzoyl peroxide gel. The primary outcome was to compare signs and symptoms of tolerability during the first two weeks of treatment using an investigator-assessed 4-point rating scale. Secondary endpoints included assessment of acne severity (Investigator Static Global Assessment and lesion counts), quality of life, product acceptability/preference, and patient assessments of tolerability and safety. Results: Of the 76 subjects enrolled in the two studies, 72 completed them. Overall both products were well tolerated, but mean scores for erythema, dryness, and peeling were significantly higher with adapalene/benzoyl peroxide gel than with clindamycin/benzoyl peroxide gel at both Weeks 1 and 2 (p<0.03). Patients also rated clindamycin/benzoyl peroxide gel significantly more tolerable than adapalene/benzoyl peroxide gel for redness, dryness, burning, itching, and scaling at Weeks 1 and 2 (p 0.0073). Mean Investigator Static Global Assessment score improved with both products during the first two weeks of treatment and continued to show significant improvement versus baseline when treatment with clindamycin/benzoyl peroxide gel was continued for a further six weeks (p<0.001 at Week 8). Lesion counts improved throughout the study with significant reductions from baseline occurring at Weeks 5 and 8 (p<0.0001 for both time points for total lesion counts). Clindamycin/benzoyl peroxide gel and adapalene/benzoyl peroxide gel were well tolerated, with most adverse events of mild-to-moderate severity. Conclusion: Clindamycin/benzoyl peroxide gel had better tolerability with regard to erythema, dryness, and peeling than adapalene/benzoyl peroxide gel during the first two weeks of treatment. PMID:22808305

A controlled, randomized, head-to-head comparison of the Prolieve thermodilatation System versus the Targis System for benign prostatic hyperplasia: safety, procedural tolerability, and clinical results.

PubMed

Shore, Neal D; Sethi, Parminder S

2010-09-01

Compare safety and tolerability of the Prolieve(®) System with the Targis(®) System using objective and subjective measures. Thirty-four men with symptomatic benign prostatic hyperplasia (BPH) were randomized to a single treatment with either the Prolieve or Targis system; 30 were treated and then followed for 6 months. After post-treatment bladder fill with ≥200 mL saline, patients were catheterized if they could not void after 2 hours or had a postvoid residual >150 mL. Catheter use, visual analog scale (VAS) tolerability scores, American Urological Association scores, and safety were assessed. After treatment, 15/16 (94%) Prolieve patients remained catheter-free compared with 3/14 (21%) Targis patients (P = 0.0001). Foley catheter indwelling time was 58.8 hours for the one Prolieve patient compared with 103.9 hrs (range 54-270 h) for the Targis patients (n = 9). Targis patients' catheterization requirements were: Seven Foley only, two intermittent self-catheters only, and two needing both. Intermittent self-catheterization continued for 1 month in two Targis patients. VAS tolerability scores were 24% to 50% lower during Prolieve treatment vs Targis (P < 0.05). Mean AUA scores for Prolieve improved from 21.2 at baseline to 12.3 and 7.9 at week 2 and month 6, respectively; for Targis, AUA scores improved from 22.9 at baseline to 17.9 and 10.9, respectively (P > 0.05). Overall, the incidence of device-related adverse events was 31% (Prolieve) compared with 64% (Targis) (P > 0.05)-most prevalently, urinary retention, dysuria, and hematuria. No device-related serious adverse events occurred. Prolieve provided enhanced near-term therapeutic benefit over Targis as assessed by catheterization, tolerability, and symptom relief, which may assist physician and patient decision-making when selecting an office-based transurethral microwave therapy option for patients.

Double overexpression of DREB and PIF transcription factors improves drought stress tolerance and cell elongation in transgenic plants.

PubMed

Kudo, Madoka; Kidokoro, Satoshi; Yoshida, Takuya; Mizoi, Junya; Todaka, Daisuke; Fernie, Alisdair R; Shinozaki, Kazuo; Yamaguchi-Shinozaki, Kazuko

2017-04-01

Although a variety of transgenic plants that are tolerant to drought stress have been generated, many of these plants show growth retardation. To improve drought tolerance and plant growth, we applied a gene-stacking approach using two transcription factor genes: DEHYDRATION-RESPONSIVE ELEMENT-BINDING 1A (DREB1A) and rice PHYTOCHROME-INTERACTING FACTOR-LIKE 1 (OsPIL1). The overexpression of DREB1A has been reported to improve drought stress tolerance in various crops, although it also causes a severe dwarf phenotype. OsPIL1 is a rice homologue of Arabidopsis PHYTOCHROME-INTERACTING FACTOR 4 (PIF4), and it enhances cell elongation by activating cell wall-related gene expression. We found that the OsPIL1 protein was more stable than PIF4 under light conditions in Arabidopsis protoplasts. Transactivation analyses revealed that DREB1A and OsPIL1 did not negatively affect each other's transcriptional activities. The transgenic plants overexpressing both OsPIL1 and DREB1A showed the improved drought stress tolerance similar to that of DREB1A overexpressors. Furthermore, double overexpressors showed the enhanced hypocotyl elongation and floral induction compared with the DREB1A overexpressors. Metabolome analyses indicated that compatible solutes, such as sugars and amino acids, accumulated in the double overexpressors, which was similar to the observations of the DREB1A overexpressors. Transcriptome analyses showed an increased expression of abiotic stress-inducible DREB1A downstream genes and cell elongation-related OsPIL1 downstream genes in the double overexpressors, which suggests that these two transcription factors function independently in the transgenic plants despite the trade-offs required to balance plant growth and stress tolerance. Our study provides a basis for plant genetic engineering designed to overcome growth retardation in drought-tolerant transgenic plants. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Frost trends and their estimated impact on yield in the Australian wheatbelt.

PubMed

Zheng, Bangyou; Chapman, Scott C; Christopher, Jack T; Frederiks, Troy M; Chenu, Karine

2015-06-01

Radiant spring frosts occurring during reproductive developmental stages can result in catastrophic yield loss for wheat producers. To better understand the spatial and temporal variability of frost, the occurrence and impact of frost events on rain-fed wheat production was estimated across the Australian wheatbelt for 1957-2013 using a 0.05 ° gridded weather data set. Simulated yield outcomes at 60 key locations were compared with those for virtual genotypes with different levels of frost tolerance. Over the last six decades, more frost events, later last frost day, and a significant increase in frost impact on yield were found in certain regions of the Australian wheatbelt, in particular in the South-East and West. Increasing trends in frost-related yield losses were simulated in regions where no significant trend of frost occurrence was observed, due to higher mean temperatures accelerating crop development and causing sensitive post-heading stages to occur earlier, during the frost risk period. Simulations indicated that with frost-tolerant lines the mean national yield could be improved by up to 20% through (i) reduced frost damage (~10% improvement) and (ii) the ability to use earlier sowing dates (adding a further 10% improvement). In the simulations, genotypes with an improved frost tolerance to temperatures 1 °C lower than the current 0 °C reference provided substantial benefit in most cropping regions, while greater tolerance (to 3 °C lower temperatures) brought further benefits in the East. The results indicate that breeding for improved reproductive frost tolerance should remain a priority for the Australian wheat industry, despite warming climates. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Obese mice on a high-fat alternate-day fasting regimen lose weight and improve glucose tolerance.

PubMed

Joslin, P M N; Bell, R K; Swoap, S J

2017-10-01

Alternate-day fasting (ADF) causes body weight (BW) loss in humans and rodents. However, it is not clear that ADF while maintaining a high-fat (HF) diet results in weight loss and the accompanying improvement in control of circulating glucose. We tested the hypotheses that a high-fat ADF protocol in obese mice would result in (i) BW loss, (ii) improved glucose control, (iii) fluctuating phenotypes on 'fasted' days when compared to 'fed' days and (iv) induction of torpor on 'fasted days'. We evaluated the physiological effects of ADF in diet-induced obese mice for BW, heart rate (HR), body temperature (T b ), glucose tolerance, insulin responsiveness, blood parameters (leptin, insulin, free fatty acids) and hepatic gene expression. Diet-induced obese male C57BL/6J mice lost one-third of their pre-diet BW while on an ADF diet for 10 weeks consisting of HF food. The ADF protocol improved glucose tolerance and insulin sensitivity, although mice on a fast day were less glucose tolerant than the same mice on a fed day. ADF mice on a fast day had low circulating insulin, but had an enhanced response to an insulin-assisted glucose tolerance test, suggesting the impaired glucose tolerance may be a result of insufficient insulin production. On fed days, ADF mice were the warmest, had a high HR and displayed hepatic gene expression and circulating leptin that closely mimicked that of mice fed an ad lib HF diet. ADF mice never entered torpor as assessed by HR and T b . However, on fast days, they were the coolest, had the slowest HR, and displayed hepatic gene expression and circulating leptin that closely mimicked that of Chow-Fed mice. Collectively, the ADF regimen with a HF diet in obese mice results in weight loss, improved blood glucose control, and daily fluctuations in selected physiological and biochemical parameters in the mouse. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

Comparing salt tolerance of beet cultivars and their halophytic ancestor: consequences of domestication and breeding programmes

PubMed Central

Rozema, Jelte; Cornelisse, Danny; Zhang, Yuancheng; Li, Hongxiu; Bruning, Bas; Katschnig, Diana; Broekman, Rob; Ji, Bin; van Bodegom, Peter

2015-01-01

Salt tolerance of higher plants is determined by a complex set of traits, the timing and rate of evolution of which are largely unknown. We compared the salt tolerance of cultivars of sugar beet and their ancestor, sea beet, in hydroponic studies and evaluated whether traditional domestication and more recent breeding have changed salt tolerance of the cultivars relative to their ancestor. Our comparison of salt tolerance of crop cultivars is based on values of the relative growth rate (RGR) of the entire plant at various salinity levels. We found considerable salt tolerance of the sea beet and slightly, but significantly, reduced salt tolerance of the sugar beet cultivars. This indicates that traditional domestication by selection for morphological traits such as leaf size, beet shape and size, enhanced productivity, sugar content and palatability slightly affected salt tolerance of sugar beet cultivars. Salt tolerance among four sugar beet cultivars, three of which have been claimed to be salt tolerant, did not differ. We analysed the components of RGR to understand the mechanism of salt tolerance at the whole-plant level. The growth rate reduction at higher salinity was linked with reduced leaf area at the whole-plant level (leaf area ratio) and at the individual leaf level (specific leaf area). The leaf weight fraction was not affected by increased salinity. On the other hand, succulence and leaf thickness and the net assimilation per unit of leaf area (unit leaf rate) increased in response to salt treatment, thus partially counteracting reduced capture of light by lower leaf area. This compensatory mechanism may form part of the salt tolerance mechanism of sea beet and the four studied sugar beet cultivars. Together, our results indicate that domestication of the halophytic ancestor sea beet slightly reduced salt tolerance and that breeding for improved salt tolerance of sugar beet cultivars has not been effective. PMID:25492122

Comparative study on fermentation performance in the genome shuffled Candida versatilis and wild-type salt tolerant yeast strain.

PubMed

Qi, Wei; Guo, Hong-Lian; Wang, Chun-Ling; Hou, Li-Hua; Cao, Xiao-Hong; Liu, Jin-Fu; Lu, Fu-Ping

2017-01-01

The fermentation performance of a genome-shuffled strain of Candida versatilis S3-5, isolated for improved tolerance to salt, and wild-type (WT) strain were analysed. The fermentation parameters, such as growth, reducing sugar, ethanol, organic acids and volatile compounds, were detected during soy sauce fermentation process. The results showed that ethanol produced by the genome shuffled strain S3-5 was increasing at a faster rate and to a greater extent than WT. At the end of the fermentation, malic acid, citric acid and succinic acid formed in tricarboxylic acid cycle after S3-5 treatment elevated by 39.20%, 6.85% and 17.09% compared to WT, respectively. Moreover, flavour compounds such as phenethyl acetate, ethyl vanillate, ethyl acetate, isoamyl acetate, ethyl myristate, ethyl pentadecanoate, ethyl palmitate and phenylacetaldehyde produced by S3-5 were 2.26, 2.12, 2.87, 34.41, 6.32, 13.64, 2.23 and 78.85 times as compared to WT. S3-5 exhibited enhanced metabolic ability as compared to the wild-type strain, improved conversion of sugars to ethanol, metabolism of organic acid and formation of volatile compounds, especially esters, Moreover, S3-5 might be an ester-flavour type salt-tolerant yeast. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Cinnamic acid exerts anti-diabetic activity by improving glucose tolerance in vivo and by stimulating insulin secretion in vitro.

PubMed

Hafizur, Rahman M; Hameed, Abdul; Shukrana, Mishkat; Raza, Sayed Ali; Chishti, Sidra; Kabir, Nurul; Siddiqui, Rehan A

2015-02-15

Although the anti-diabetic activity of cinnamic acid, a pure compound from cinnamon, has been reported but its mechanism(s) is not yet clear. The present study was designed to explore the possible mechanism(s) of anti-diabetic activity of cinnamic acid in in vitro and in vivo non-obese type 2 diabetic rats. Non-obese type 2 diabetes was developed by injecting 90 mg/kg streptozotocin in 2-day-old Wistar pups. Cinnamic acid and cinnamaldehyde were administered orally to diabetic rats for assessing acute blood glucose lowering effect and improvement of glucose tolerance. Additionally, insulin secretory activity of cinnamic acid and cinnamaldehyde was evaluated in isolated mice islets. Cinnamic acid, but not cinnamaldehyde, decreased blood glucose levels in diabetic rats in a time- and dose-dependent manner. Oral administration of cinnamic acid with 5 and 10 mg/kg doses to diabetic rats improved glucose tolerance in a dose-dependent manner. The improvement by 10 mg/kg cinnamic acid was comparable to that of standard drug glibenclamide (5 mg/kg). Further in vitro studies showed that cinnamaldehyde has little or no effect on glucose-stimulated insulin secretion; however, cinnamic acid significantly enhanced glucose-stimulated insulin secretion in isolated islets. In conclusion, it can be said that cinnamic acid exerts anti-diabetic activity by improving glucose tolerance in vivo and stimulating insulin secretion in vitro. Copyright © 2015 Elsevier GmbH. All rights reserved.

Open-label study assessing the efficacy and tolerability of topical skincare and sun protection products following intense pulsed light treatment.

PubMed

Jones, Isabela T; Guiha, Isabella; Fabi, Sabrina G

2017-11-21

The visible signs of photodamage can be improved by intense pulsed light (IPL). Active ingredients in cosmeceuticals also have effects on skin quality and pigmentation, and can camouflage post-treatment side effects. Combination therapies utilizing different treatment modalities have been shown to optimize clinical outcomes for skin rejuvenation and patient satisfaction. To evaluate the efficacy of a combination of IPL with a daily topical skincare and sunscreen regimen for the treatment of facial photodamage and for the improvement of IPL treatment tolerability. Twenty female subjects with moderate-to-severe facial photodamage, with past history of IPL treatments, received one IPL treatment followed by the use of the topical skincare regimen for 8 weeks. An investigator assessed facial photodamage and hyperpigmentation at baseline, week 4, and week 8, and postprocedure erythema. Subject questionnaires were also administered at each visit. Compared to baseline, there was a significant improvement in photodamage and hyperpigmentation of bare facial skin. The application of the skincare regimen resulted in a significant reduction in post-IPL erythema, stinging/burning, and itching. The majority of patients were very satisfied or satisfied and felt the treatment regimen improved various aspects of skin quality and the tolerability of the procedure. The addition of a topical skincare regimen after IPL treatment to the face resulted in significant improvements in facial photodamage and pigmentation, decreased post-treatment side effects, and increased tolerability. © 2017 Wiley Periodicals, Inc.

Effectiveness of ketamine as an adjuvant to opioid-based therapy in decreasing pain associated with opioid tolerance in adults undergoing orthopedic surgery: a systematic review protocol.

PubMed

Bennett, Marsha; Bonanno, Laura; Kuhn, William

2016-10-01

The objective of this systematic review is to examine the best available evidence on the clinical effectiveness of ketamine as an adjuvant to opioid-based therapy versus opioid-based therapy alone in decreasing perioperative pain associated with opioid tolerance in adult patients, aged 18-70 years, undergoing orthopedic surgical procedures.The following question guides the systematic review: does the administration of ketamine as an adjuvant to opioid-based therapy, compared to opioid-based therapy alone, improve perioperative pain relief in opioid-tolerant adult patients undergoing orthopedic surgical procedures?

Systems biology approach in plant abiotic stresses.

PubMed

Mohanta, Tapan Kumar; Bashir, Tufail; Hashem, Abeer; Abd Allah, Elsayed Fathi

2017-12-01

Plant abiotic stresses are the major constraint on plant growth and development, causing enormous crop losses across the world. Plants have unique features to defend themselves against these challenging adverse stress conditions. They modulate their phenotypes upon changes in physiological, biochemical, molecular and genetic information, thus making them tolerant against abiotic stresses. It is of paramount importance to determine the stress-tolerant traits of a diverse range of genotypes of plant species and integrate those traits for crop improvement. Stress-tolerant traits can be identified by conducting genome-wide analysis of stress-tolerant genotypes through the highly advanced structural and functional genomics approach. Specifically, whole-genome sequencing, development of molecular markers, genome-wide association studies and comparative analysis of interaction networks between tolerant and susceptible crop varieties grown under stress conditions can greatly facilitate discovery of novel agronomic traits that protect plants against abiotic stresses. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Meropenem: an updated review of its use in the management of intra-abdominal infections.

PubMed

Lowe, M N; Lamb, H M

2000-09-01

Meropenem is a carbapenem antibacterial agent with a broad spectrum of activity which encompasses gram-negative, gram-positive and anaerobic bacteria. Like other carbapenems, meropenem is stable against chromosomal and extended-spectrum beta-lactamases. In patients with moderate to severe intra-abdominal infections, empirical monotherapy with meropenem achieved clinical response rates ranging from 91 to 100% in 7 randomised comparative trials. Efficacy rates were similar to those of imipenem/cilastatin (94 to 97%), clindamycin plus tobramycin (93%) and, overall, to cefotaxime plus metronidazole (75 to 100%), although there were differences between trials versus this combination regimen. According to limited data, meropenem also achieved clinical response rates of over 80% in patients with severe intra-abdominal infections. Meropenem is well tolerated, the most common adverse events being diarrhoea, rash, nausea/vomiting and inflammation at the injection site which are reported in <2.5% of patients each. Meropenem also has an improved CNS tolerability profile compared with imipenem/cilastatin. Extensive comparative clinical data demonstrate that meropenem can be used effectively as empirical monotherapy in moderate to severe intra-abdominal infections. It also shows potential in the most severe forms of infection, although experience in this infection type remains limited. Compared with standard combination regimens, meropenem offers the benefits of ease of administration without the need for monitoring. It also offers improved CNS tolerability compared with imipenem/cilastatin with the option of a higher maximum dosage, which may be a particular advantage in patients with severe intra-abdominal infections.

The membrane tethered transcription factor EcbZIP17 from finger millet promotes plant growth and enhances tolerance to abiotic stresses.

PubMed

Ramakrishna, Chopperla; Singh, Sonam; Raghavendrarao, Sangala; Padaria, Jasdeep C; Mohanty, Sasmita; Sharma, Tilak Raj; Solanke, Amolkumar U

2018-02-01

The occurrence of various stresses, as the outcome of global climate change, results in the yield losses of crop plants. Prospecting of genes in stress tolerant plant species may help to protect and improve their agronomic performance. Finger millet (Eleusine coracana L.) is a valuable source of superior genes and alleles for stress tolerance. In this study, we isolated a novel endoplasmic reticulum (ER) membrane tethered bZIP transcription factor from finger millet, EcbZIP17. Transgenic tobacco plants overexpressing this gene showed better vegetative growth and seed yield compared with wild type (WT) plants under optimal growth conditions and confirmed upregulation of brassinosteroid signalling genes. Under various abiotic stresses, such as 250 mM NaCl, 10% PEG6000, 400 mM mannitol, water withdrawal, and heat stress, the transgenic plants showed higher germination rate, biomass, primary and secondary root formation, and recovery rate, compared with WT plants. The transgenic plants exposed to an ER stress inducer resulted in greater leaf diameter and plant height as well as higher expression of the ER stress-responsive genes BiP, PDIL, and CRT1. Overall, our results indicated that EcbZIP17 improves plant growth at optimal conditions through brassinosteroid signalling and provide tolerance to various environmental stresses via ER signalling pathways.

Efficacy and Cost-Effectiveness Analysis of Evidence-Based Nursing Interventions to Maintain Tissue Integrity to Prevent Pressure Ulcers and Incontinence-Associated Dermatitis.

PubMed

Avşar, Pınar; Karadağ, Ayişe

2018-02-01

A reduction in tissue tolerance promotes the development of pressure ulcers (PUs) and incontinence-associated dermatitis (IAD). To determine the cost-effectiveness and efficacy of evidence-based (EB) nursing interventions on increasing tissue tolerance by maintaining tissue integrity. The study involved 154 patients in two intensive care units (77 patients, control group; 77 patients, intervention group). Data were collected using the following: patient characteristics form, Braden PU risk assessment scale, tissue integrity monitoring form, PU identification form, IAD and severity scale, and a cost table of the interventions. Patients in the intervention group were cared for by nurses trained in the use of the data collection tools and in EB practices to improve tissue tolerance. Routine nursing care was given to the patients in the control group. The researcher observed all patients in terms of tissue integrity and recorded the care-related costs. Deterioration of tissue integrity was observed in 18.2% patients in the intervention group compared to 54.5% in the control group (p < .05). The average cost to increase tissue tolerance prevention in the intervention and control groups was X¯ = $204.34 ± 41.07 and X¯ = $138.90 ± 1.70, respectively. It is recommended that EB policies and procedures are developed to improve tissue tolerance by maintaining tissue integrity. Although the cost of EB preventive initiatives is relatively high compared to those that are not EB, the former provide a significant reduction in the prevalence of tissue integrity deterioration. © 2017 Sigma Theta Tau International.

Controlled release of Lactobacillus rhamnosus biofilm probiotics from alginate-locust bean gum microcapsules.

PubMed

Cheow, Wean Sin; Kiew, Tie Yi; Hadinoto, Kunn

2014-03-15

Chitosan-coated alginate microcapsules containing high-density biofilm Lactobacillus rhamnosus have been previously shown to exhibit higher freeze drying- and thermal-tolerance than their planktonic counterparts. However, their cell release profile remains poor due to the capsules' susceptibility to the gastric environment. Herein the effects of adding locust bean (LB) and xanthan (XT) gums to alginate (AGN) capsules on the stress tolerance and cell release profiles in simulated gastrointestinal fluids are investigated. Compared to the AGN-only capsules, the AGN-LB capsules exhibit improved stress tolerance (i.e. ≈ 6x for freeze drying, 100x for thermotolerance, 10x for acid), whereas the AGN-XT capsules only improve the acid tolerance. Importantly, the AGN-LB capsules possess the optimal cell release profile with a majority of cells released in the simulated intestinal juice than in the gastric juice. The AGN-LB capsules' superiority is attributed to their stronger interaction with the chitosan coating and high swelling capacity, thus delaying their bulk dissolution. Copyright © 2014 Elsevier Ltd. All rights reserved.

Point mutation of H3/H4 histones affects acetic acid tolerance in Saccharomyces cerevisiae.

PubMed

Liu, Xiangyong; Zhang, Xiaohua; Zhang, Zhaojie

2014-10-10

The molecular mechanism of acetic acid tolerance in yeast remains unclear despite of its importance for efficient cellulosic ethanol production. In this study, we examined the effects of histone H3/H4 point mutations on yeast acetic acid tolerance by comprehensively screening a histone H3/H4 mutant library. A total of 24 histone H3/H4 mutants (six acetic acid resistant and 18 sensitive) were identified. Compared to the wild-type strain, the histone acetic acid-resistant mutants exhibited improved ethanol fermentation performance under acetic acid stress. Genome-wide transcriptome analysis revealed that changes in the gene expression in the acetic acid-resistant mutants H3 K37A and H4 K16Q were mainly related to energy production, antioxidative stress. Our results provide novel insights into yeast acetic acid tolerance on the basis of histone, and suggest a novel approach to improve ethanol production by altering the histone H3/H4 sequences. Copyright © 2014 Elsevier B.V. All rights reserved.

Changes in SBPase activity influence photosynthetic capacity, growth, and tolerance to chilling stress in transgenic tomato plants

PubMed Central

Ding, Fei; Wang, Meiling; Zhang, Shuoxin; Ai, Xizhen

2016-01-01

Sedoheptulose-1, 7-bisphosphatase (SBPase) is an important enzyme involved in photosynthetic carbon fixation in the Calvin cycle. Here, we report the impact of changes in SBPase activity on photosynthesis, growth and development, and chilling tolerance in SBPase antisense and sense transgenic tomato (Solanum lycopersicum) plants. In transgenic plants with increased SBPase activity, photosynthetic rates were increased and in parallel an increase in sucrose and starch accumulation was evident. Total biomass and leaf area were increased in SBPase sense plants, while they were reduced in SBPase antisense plants compared with equivalent wild-type tomato plants. Under chilling stress, when compared with plants with decreased SBPase activity, tomato plants with increased SBPase activity were found to be more chilling tolerant as indicated by reduced electrolyte leakage, increased photosynthetic capacity, and elevated RuBP regeneration rate and quantum efficiency of photosystem II. Collectively, our data suggest that higher level of SBPase activity gives an advantage to photosynthesis, growth and chilling tolerance in tomato plants. This work also provides a case study that an individual enzyme in the Calvin cycle may serve as a useful target for genetic engineering to improve production and stress tolerance in crops. PMID:27586456

Drought Tolerance during Reproductive Development is Important for Increasing wheat yield Potential under Climate change in Europe.

PubMed

Senapati, Nimai; Stratonovitch, Pierre; Paul, Matthew J; Semenov, Mikhail A

2018-06-12

Drought stress during reproductive development could drastically reduce grain number and wheat yield, but quantitative evaluation of such effect is unknown under climate change. The objectives of this study were to a) evaluate potential yield benefits of drought tolerance during reproductive development for wheat ideotypes under climate change in Europe, and b) identify potential cultivar parameters for improvement. We used the Sirius wheat model to optimise drought tolerant (DT) and drought sensitive (DS) wheat ideotypes under future 2050 climate scenario at 13 contrasting sites, representing major wheat growing regions in Europe. Averaged over the sites, DT ideotypes achieved 13.4% greater yield compared to DS, with the double yield stability for DT. However, the performances of the ideotypes were site dependent. Mean yield of DT was 28-37% greater compared to DS in southern Europe. In contrast, no yield difference (≤ 1%) between ideotypes was found in north-western Europe. An intermediate yield benefit of 10-23% was found due to drought tolerance in central and eastern Europe. We conclude that tolerance to drought stress during reproductive development is important for high yield potentials and greater yield stability of wheat under climate change in Europe.

The sunflower transcription factor HaWRKY76 confers drought and flood tolerance to Arabidopsis thaliana plants without yield penalty.

PubMed

Raineri, Jesica; Ribichich, Karina F; Chan, Raquel L

2015-12-01

Arabidopsis transgenic plants expressing the sunflower transcription factor HaWRKY76 exhibit increased yield and tolerance to drought and flood stresses. The genetic construct containing HaWRKY76 is proposed as a potential biotechnological tool to improve crops. Water deficit and water excess are abiotic stress factors that seriously affect crops worldwide. To increase the tolerance to such stresses without causing yield penalty constitutes a major goal for biotechnologists. In this survey, we report that HaWRKY76, a divergent sunflower WRKY transcription factor, is able to confer both dehydration and submergence tolerance to Arabidopsis transgenic plants without yield penalty. The expression pattern of HaWRKY76 was analyzed in plants grown in standard conditions and under different watering regimes indicating a regulation by water availability. The corresponding cDNA was isolated and cloned under the control of a constitutive promoter and Arabidopsis plants were transformed with this construct. These transgenic plants presented higher biomass, seed production and sucrose content than controls in standard growth conditions. Moreover, they exhibited tolerance to mild drought or flood (complete submergence/waterlogging) stresses as well as the same or increased yield, depending on the stress severity and plant developmental stage, compared with controls. Drought tolerance occurred via an ABA-independent mechanism and induction of stomatal closure. Submergence tolerance can be explained by the carbohydrate (sucrose and starch) preservation achieved through the repression of fermentation pathways. Higher cell membrane stability and chlorenchyma maintenance could be the nexus between tolerance responses in front of both stresses. Altogether, the obtained results indicated that HaWRKY76 can be a potential biotechnological tool to improve crops yield as well as drought and flood tolerances.

Evidence of cyclical light/dark-regulated expression of freezing tolerance in young winter wheat plants.

PubMed

Skinner, Daniel Z; Bellinger, Brian; Hiscox, William; Helms, Gregory L

2018-01-01

The ability of winter wheat (Triticum aestivum L.) plants to develop freezing tolerance through cold acclimation is a complex rait that responds to many environmental cues including day length and temperature. A large part of the freezing tolerance is conditioned by the C-repeat binding factor (CBF) gene regulon. We investigated whether the level of freezing tolerance of 12 winter wheat lines varied throughout the day and night in plants grown under a constant low temperature and a 12-hour photoperiod. Freezing tolerance was significantly greater (P<0.0001) when exposure to subfreezing temperatures began at the midpoint of the light period, or the midpoint of the dark period, compared to the end of either period, with an average of 21.3% improvement in survival. Thus, freezing survival was related to the photoperiod, but cycled from low, to high, to low within each 12-hour light period and within each 12-hour dark period, indicating ultradian cyclic variation of freezing tolerance. Quantitative real-time PCR analysis of expression levels of CBF genes 14 and 15 indicated that expression of these two genes also varied cyclically, but essentially 180° out of phase with each other. Proton nuclear magnetic resonance analysis (1H-NMR) showed that the chemical composition of the wheat plants' cellular fluid varied diurnally, with consistent separation of the light and dark phases of growth. A compound identified as glutamine was consistently found in greater concentration in a strongly freezing-tolerant wheat line, compared to moderately and poorly freezing-tolerant lines. The glutamine also varied in ultradian fashion in the freezing-tolerant wheat line, consistent with the ultradian variation in freezing tolerance, but did not vary in the less-tolerant lines. These results suggest at least two distinct signaling pathways, one conditioning freezing tolerance in the light, and one conditioning freezing tolerance in the dark; both are at least partially under the control of the CBF regulon.

Influence of Pulmonary Rehabilitation on Lung Function Changes After the Lung Resection for Primary Lung Cancer in Patients with Chronic Obstructive Pulmonary Disease.

PubMed

Mujovic, Natasa; Mujovic, Nebojsa; Subotic, Dragan; Ercegovac, Maja; Milovanovic, Andjela; Nikcevic, Ljubica; Zugic, Vladimir; Nikolic, Dejan

2015-11-01

Influence of physiotherapy on the outcome of the lung resection is still controversial. Study aim was to assess the influence of physiotherapy program on postoperative lung function and effort tolerance in lung cancer patients with chronic obstructive pulmonary disease (COPD) that are undergoing lobectomy or pneumonectomy. The prospective study included 56 COPD patients who underwent lung resection for primary non small-cell lung cancer after previous physiotherapy (Group A) and 47 COPD patients (Group B) without physiotherapy before lung cancer surgery. In Group A, lung function and effort tolerance on admission were compared with the same parameters after preoperative physiotherapy. Both groups were compared in relation to lung function, effort tolerance and symptoms change after resection. In patients with tumors requiring a lobectomy, after preoperative physiotherapy, a highly significant increase in FEV1, VC, FEF50 and FEF25 of 20%, 17%, 18% and 16% respectively was registered with respect to baseline values. After physiotherapy, a significant improvement in 6-minute walking distance was achieved. After lung resection, the significant loss of FEV1 and VC occurred, together with significant worsening of the small airways function, effort tolerance and symptomatic status. After the surgery, a clear tendency existed towards smaller FEV1 loss in patients with moderate to severe, when compared to patients with mild baseline lung function impairment. A better FEV1 improvement was associated with more significant loss in FEV1. Physiotherapy represents an important part of preoperative and postoperative treatment in COPD patients undergoing a lung resection for primary lung cancer.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sardi, Maria; Rovinskiy, Nikolay; Zhang, Yaoping

We report a major obstacle to sustainable lignocellulosic biofuel production is microbe inhibition by the combinatorial stresses in pretreated plant hydrolysate. Chemical biomass pretreatment releases a suite of toxins that interact with other stressors, including high osmolarity and temperature, which together can have poorly understood synergistic effects on cells. Improving tolerance in industrial strains has been hindered, in part because the mechanisms of tolerance reported in the literature often fail to recapitulate in other strain backgrounds. Here, we explored and then exploited variations in stress tolerance, toxin-induced transcriptomic responses, and fitness effects of gene overexpression in different Saccharomyces cerevisiae (yeast)more » strains to identify genes and processes linked to tolerance of hydrolysate stressors. Using six different S. cerevisiae strains that together maximized phenotypic and genetic diversity, first we explored transcriptomic differences between resistant and sensitive strains to identify common and strain-specific responses. This comparative analysis implicated primary cellular targets of hydrolysate toxins, secondary effects of defective defense strategies, and mechanisms of tolerance. Dissecting the responses to individual hydrolysate components across strains pointed to synergistic interactions between osmolarity, pH, hydrolysate toxins, and nutrient composition. By characterizing the effects of high-copy gene overexpression in three different strains, we revealed the breadth of the background-specific effects of gene fitness contributions in synthetic hydrolysate. Lastly, our approach identified new genes for engineering improved stress tolerance in diverse strains while illuminating the effects of genetic background on molecular mechanisms.« less

Enhancement of geraniol resistance of Escherichia coli by MarA overexpression.

PubMed

Shah, Asad Ali; Wang, Chonglong; Chung, Young-Ryun; Kim, Jae-Yean; Choi, Eui-Sung; Kim, Seon-Won

2013-03-01

Improvement of a microorganism's tolerance against organic solvents is required for a microbial factory producing terpenoid based biofuels. The bacterial genes, marA, imp, cls and cti have been found to increase organic solvent tolerance. Thus, the tolerance against the following terpenoids (isopentenol, geraniol, myrcene, and farnesol) was studied with overexpression of marA, imp, cls and cti genes in Escherichia coli. The marA overexpression significantly enhanced the tolerance of E. coli against geraniol, whereas there was no tolerance improvement against the terpenoids by overexpression of cls and cti genes. The imp overexpression even yielded sensitive phenotype to the tested solvents. The colony forming efficiency of the marA overexpressing E. coli was increased by 10(4)-fold in plate overlay of geraniol compared to that of wild type E. coli and a two-fold decrease of intracellular geraniol accumulation was also observed in liquid culture of geraniol. Single knock-out mutations of marA, or one of the following genes (acrA, acrB and tolC) encoding AcrAB-TolC efflux pump made E. coli hypersensitive to geraniol. The geraniol tolerance conferred by marA overexpression was attributed to the AcrAB-TolC efflux pump that is activated by MarA. Copyright © 2012 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Dose-dependent response of Trichoderma harzianum in improving drought tolerance in rice genotypes.

PubMed

Pandey, Veena; Ansari, Mohammad W; Tula, Suresh; Yadav, Sandep; Sahoo, Ranjan K; Shukla, Nandini; Bains, Gurdeep; Badal, Shail; Chandra, Subhash; Gaur, A K; Kumar, Atul; Shukla, Alok; Kumar, J; Tuteja, Narendra

2016-05-01

This study demonstrates a dose-dependent response of Trichoderma harzianum Th-56 in improving drought tolerance in rice by modulating proline, SOD, lipid peroxidation product and DHN / AQU transcript level, and the growth attributes. In the present study, the effect of colonization of different doses of T. harzianum Th-56 strain in rice genotypes were evaluated under drought stress. The rice genotypes treated with increasing dose of T. harzianum strain Th-56 showed better drought tolerance as compared with untreated control plant. There was significant change in malondialdehyde, proline, higher superoxide dismutase level, plant height, total dry matter, relative chlorophyll content, leaf rolling, leaf tip burn, and the number of scorched/senesced leaves in T. harzianum Th-56 treated rice genotypes under drought stress. This was corroborated with altered expression of aquaporin and dehydrin genes in T. harzianum Th-56 treated rice genotypes. The present findings suggest that a dose of 30 g/L was the most effective in improving drought tolerance in rice, and its potential exploitation will contribute to the advancement of rice genotypes to sustain crop productivity under drought stress. Interaction studies of T. harzianum with three aromatic rice genotypes suggested that PSD-17 was highly benefitted from T. harzianum colonization under drought stress.

Exogenous application of plant growth regulators (PGRs) induces chilling tolerance in short-duration hybrid maize.

PubMed

Waqas, Muhammad Ahmed; Khan, Imran; Akhter, Muhammad Javaid; Noor, Mehmood Ali; Ashraf, Umair

2017-04-01

Chilling stress hampers the optimal performance of maize under field conditions precipitously by inducing oxidative stress. To confer the damaging effects of chilling stress, the present study aimed to investigate the effects of some natural and synthetic plant growth regulators, i.e., salicylic acid (SA), thiourea (TU), sorghum water extract (SWE), and moringa leaf extract (MLE) on chilling stress tolerance in autumn maize hybrid. Foliar application of growth regulators at low concentrations was carried out at six leaf (V6) and tasseling stages. An increase in crop growth rate (CGR), leaf area index (LAI), leaf area duration (LAD), plant height (PH), grain yield (GY), and total dry matter accumulation (TDM) was observed in exogenously applied plants as compared to control. In addition, improved physio-biochemical, phenological, and grain nutritional quality attributes were noticed in foliar-treated maize plots as compared to non-treated ones. SA-treated plants reduced 20% electrolyte leakage in cell membrane against control. MLE and SA were proved best in improving total phenolic, relative water (19-23%), and chlorophyll contents among other applications. A similar trend was found for photosynthetic and transpiration rates, whereas MLE and SWE were found better in improving CGR, LAI, LAD, TDM, PH, GY, grains per cob, 1000 grain weight, and biological yield among all treatments including control. TU and MLE have significantly reduced the duration in phenological events of crop at the reproductive stage. MLE, TU, and SA also improved the grain protein, oil, and starch contents as compared to control. Enhanced crop water productivity was also observed in MLE-treated plants. Economic analysis suggested that MLE and SA applications were more economical in inducing chilling stress tolerance under field conditions. Although eliciting behavior of all growth regulators improved morpho-physiological attributes against suboptimal temperature stress conditions, MLE and SA acted as leading agents which proved to be better stress alleviators by improving plant physio-biochemical attributes and maize growth.

Inhibition of adipose tissue PPARγ prevents increased adipocyte expansion after lipectomy and exacerbates a glucose-intolerant phenotype.

PubMed

Booth, A D; Magnuson, A M; Cox-York, K A; Wei, Y; Wang, D; Pagliassotti, M J; Foster, M T

2017-04-01

Adipose tissue plays a fundamental role in glucose homeostasis. For example, fat removal (lipectomy, LipX) in lean mice, resulting in a compensatory 50% increase in total fat mass, is associated with significant improvement in glucose tolerance. This study was designed to further examine the link between fat removal, adipose tissue compensation and glucose homeostasis using a peroxisome proliferator-activated receptor γ (PPAR γ; activator of adipogenesis) knockout mouse. The study involved PPARγ knockout (FKOγ) or control mice (CON), subdivided into groups that received LipX or Sham surgery. We reasoned that as the ability of adipose tissue to expand in response to LipX would be compromised in FKOγ mice, so would improvements in glucose homeostasis. In CON mice, LipX increased total adipose depot mass (~60%), adipocyte number (~45%) and changed adipocyte distribution to smaller cells. Glucose tolerance was improved (~30%) in LipX CON mice compared to Shams. In FKOγ mice, LipX did not result in any significant changes in adipose depot mass, adipocyte number or distribution. LipX FKOγ mice were also characterized by reduction of glucose tolerance (~30%) compared to shams. Inhibition of adipose tissue PPARγ prevented LipX-induced increases in adipocyte expansion and produced a glucose-intolerant phenotype. These data support the notion that adipose tissue expansion is critical to maintain and/or improvement in glucose homeostasis. © 2016 John Wiley & Sons Ltd.

Removal of intra-abdominal visceral adipose tissue improves glucose tolerance in rats: role of hepatic triglyceride storage.

PubMed

Foster, Michelle T; Shi, Haifei; Seeley, Randy J; Woods, Stephen C

2011-10-24

Epidemiological studies have demonstrated a strong link between increased visceral fat and metabolic syndrome. In rodents, removal of intra-abdominal but non-visceral fat improves insulin sensitivity and glucose homeostasis, though previous studies make an imprecise comparison to human physiology because actual visceral fat was not removed. We hypothesize that nutrient release from visceral adipose tissue may have greater consequences on metabolic regulation than nutrient release from non-visceral adipose depots since the latter drains into systemic but not portal circulation. To assess this we surgically decreased visceral white adipose tissue (~0.5 g VWATx) and compared the effects to removal of non-visceral epididymal fat (~4 g; EWATx), combination removal of visceral and non-visceral fat (~4.5 g; EWATx/VWATx) and sham-operated controls, in chow-fed rats. At 8 weeks after surgery, only the groups with visceral fat removed had a significantly improved glucose tolerance, although 8 times more fat was removed in EWATx compared with VWATx. This suggests that mechanisms controlling glucose metabolism are relatively more sensitive to reductions in visceral adipose tissue mass. Groups with visceral fat removed also had significantly decreased hepatic lipoprotein lipase (LPL) and triglyceride content compared with controls, while carnitine palmitoyltransferase (CPT-1A) was decreased in all fat-removal groups. In a preliminary experiment, we assessed the opposite hypothesis; i.e., we transplanted excess visceral fat from a donor rat to the visceral cavity (omentum and mesentery), which drains into the hepatic portal vein, of a recipient rat but observed no major metabolic effect. Overall, our results indicate surgical removal of intra-abdominal fat improves glucose tolerance through mechanism that may be mediated by reductions in liver triglyceride. Published by Elsevier Inc.

Removal of Intra-abdominal Visceral Adipose Tissue Improves Glucose Tolerance in Rats: Role of Hepatic Triglyceride Storage

PubMed Central

Foster, Michelle T.; Shi, Haifei; Seeley, Randy J.; Woods, Stephen C.

2011-01-01

Epidemiological studies have demonstrated a strong link between increased visceral fat and metabolic syndrome. In rodents, removal of intra-abdominal but non-visceral fat improves insulin sensitivity and glucose homeostasis, though previous studies make an imprecise comparison to human physiology because actual visceral fat was not removed. We hypothesize that nutrient release from visceral adipose tissue may have greater consequences on metabolic regulation than nutrient release from non-visceral adipose depots since the latter drains into systemic but not portal circulation. To assess this we surgically decreased visceral white adipose tissue (~0.5 g VWATx) and compared the effects to removal of non-visceral epididymal fat (~4 g; EWATx), combination removal of visceral and non-visceral fat (~4.5 g; EWATx/VWATx) and sham-operated controls, in chow-fed rats. At 8 weeks after surgery, only the groups with visceral fat removed had a significantly improved glucose tolerance, although 8 times more fat was removed in EWATx compared with VWATx. This suggests that mechanisms controlling glucose metabolism are relatively more sensitive to reductions in visceral adipose tissue mass. Groups with visceral fat removed also had significantly decreased hepatic lipoprotein lipase (LPL) and triglyceride content compared with controls, while carnitine palmitoyltransferase (CPT-1A) was decreased in all fat-removal groups. In a preliminary experiment, we assessed the opposite hypothesis; i.e., we transplanted excess visceral fat from a donor rat to the visceral cavity (omentum and mesentery), which drains into the hepatic portal vein, of a recipient rat but observed no major metabolic effect. Overall, our results indicate surgical removal of intra-abdominal fat improves glucose tolerance through mechanism that may be mediated by reductions in liver triglyceride. PMID:21683727

Effect of saturated fatty acid-rich dietary vegetable oils on lipid profile, antioxidant enzymes and glucose tolerance in diabetic rats

PubMed Central

Kochikuzhyil, Benson Mathai; Devi, Kshama; Fattepur, Santosh Raghunandan

2010-01-01

Objective: To study the effect of saturated fatty acid (SFA)-rich dietary vegetable oils on the lipid profile, endogenous antioxidant enzymes and glucose tolerance in type 2 diabetic rats. Materials and Methods: Type 2 diabetes was induced by administering streptozotocin (90 mg/kg, i.p.) in neonatal rats. Twenty-eight-day-old normal (N) and diabetic (D) male Wistar rats were fed for 45 days with a fat-enriched special diet (10%) prepared with coconut oil (CO) – lauric acid-rich SFA, palm oil (PO) – palmitic acid-rich SFA and groundnut oil (GNO) – control (N and D). Lipid profile, endogenous antioxidant enzymes and oral glucose tolerance tests were monitored. Results: D rats fed with CO (D + CO) exhibited a significant decrease in the total cholesterol and non-high-density lipoprotein cholesterol. Besides, they also showed a trend toward improving antioxidant enzymes and glucose tolerance as compared to the D + GNO group, whereas D + PO treatment aggravated the dyslipidemic condition while causing a significant decrease in the superoxide dismutase levels when compared to N rats fed with GNO (N + GNO). D + PO treatment also impaired the glucose tolerance when compared to N + GNO and D + GNO. Conclusion: The type of FA in the dietary oil determines its deleterious or beneficial effects. Lauric acid present in CO may protect against diabetes-induced dyslipidemia. PMID:20871763

Depth optimal sorting networks resistant to k passive faults

DOE Office of Scientific and Technical Information (OSTI.GOV)

Piotrow, M.

In this paper, we study the problem of constructing a sorting network that is tolerant to faults and whose running time (i.e. depth) is as small as possible. We consider the scenario of worst-case comparator faults and follow the model of passive comparator failure proposed by Yao and Yao, in which a faulty comparator outputs directly its inputs without comparison. Our main result is the first construction of an N-input, k-fault-tolerant sorting network that is of an asymptotically optimal depth {theta}(log N+k). That improves over the recent result of Leighton and Ma, whose network is of depth O(log N +more » k log log N/log k). Actually, we present a fault-tolerant correction network that can be added after any N-input sorting network to correct its output in the presence of at most k faulty comparators. Since the depth of the network is O(log N + k) and the constants hidden behind the {open_quotes}O{close_quotes} notation are not big, the construction can be of practical use. Developing the techniques necessary to show the main result, we construct a fault-tolerant network for the insertion problem. As a by-product, we get an N-input, O(log N)-depth INSERT-network that is tolerant to random faults, thereby answering a question posed by Ma in his PhD thesis. The results are based on a new notion of constant delay comparator networks, that is, networks in which each register is used (compared) only in a period of time of a constant length. Copies of such networks can be put one after another with only a constant increase in depth per copy.« less

Proposal of ICI cancellation using opposite weightings on symmetric subcarrier pairs in CO-OFDM systems

NASA Astrophysics Data System (ADS)

Zhang, Jing; Chen, Xuemei; Deng, Mingliang; Zeng, Dengke; Yang, Heming; Qiu, Kun

2015-08-01

We propose a novel ICI cancellation using opposite weighting on symmetric subcarrier pairs to combat the linear phase noise of laser source and the nonlinear phase noise resulted from the fiber nonlinearity. We compare the proposed ICI cancellation scheme with conventional OFDM and the ICI self-cancellation at the same raw bit rate of 35.6 Gb/s. In simulations, the proposed ICI cancellation scheme shows better phase noise tolerance compared with conventional OFDM and has similar phase noise tolerance with the ICI self-cancellation. The laser linewidth is about 13 MHz at BER of 2 × 10-3 with ICI cancellation scheme while it is 5 MHz in conventional OFDM. We also study the nonlinearity tolerance and find that the proposed ICI cancellation scheme is better compared with the other two schemes which due to the first order nonlinearity mitigation. The launch power is 7 dBm for the proposed ICI cancellation scheme and its SNR improves by 4 dB or 3 dB compared with the ICI self-cancellation or conventional OFDM at BER of 1.1 × 10-3, respectively.

Roles of Plasmalemma Aquaporin Gene StPIP1 in Enhancing Drought Tolerance in Potato

PubMed Central

Wang, Li; Liu, Yuhui; Feng, Shoujiang; Yang, Jiangwei; Li, Dan; Zhang, Junlian

2017-01-01

Survival and mortality of plants in response to severe drought may be related to carbon starvation, but little is known about how plasma membrane intrinsic proteins may help alleviate the drought-induced damage. Here, we determined the roles of plasmalemma aquaporin gene in improving plant water status, maintaining carbon accumulation, and thereby enhancing drought tolerance. Seven StPIP1 transformed potato (Solanum tuberosum L.) lines (namely T1, T2…T7) were compared with non-transgenic control plant at molecule and whole-plant levels. The relative expression of StPIP1 gene was found in leaves, stems and roots, with the most abundant expression being in the roots. The transgenic lines T6 and T7 had the highest StPIP1 expression, averaging 7.2 times that of the control and the greatest differences occurred 48 h after mannitol osmotic stress treatment. Using an evaluation index to quantifying the degree of drought tolerance, we found that the StPIP1 transgenic lines T6 and T7 had the highest drought tolerance, averaging 8.5 times that of the control. Measured at 30 days in drought stress treatment, the control plant decreased net photosynthetic rate by 33 and 56%, respectively, under moderate and severe stresses; also decreased stomatal conductance by 39 and 65%; and lowered transpiration rate by 49 and 69%, compared to the no-stress treatment, whereas the transgenic lines T6 and T7 maintained a relatively stable level with slight decreases in these properties. The constitutive overexpression of StPIP1 in potato improved plant water use efficiency and increased nonstructural carbohydrate concentration, which helped alleviate carbon starvation and minimized the loss of biomass and tuber yield due to drought stress. We conclude that the expression of StPIPs improves overall water relations in the plant and helps maintain photosynthesis and stomatal conductance; these help minimize carbon starvation and enhance the whole plant tolerance to drought stress. PMID:28487712

Spraying Brassinolide improves Sigma Broad tolerance in foxtail millet (Setaria italica L.) through modulation of antioxidant activity and photosynthetic capacity.

PubMed

Yuan, Xiang-Yang; Zhang, Li-Guang; Huang, Lei; Yang, Hui-Jie; Zhong, Yan-Ting; Ning, Na; Wen, Yin-Yuan; Dong, Shu-Qi; Song, Xi-E; Wang, Hong-Fu; Guo, Ping-Yi

2017-09-11

To explore the role of Brassinolide (BR) in improving the tolerance of Sigma Broad in foxtail millet (Setaria italica L.), effects of 0.1 mg/L of BR foliar application 24 h before 3.37 g/ha of Sigma Broad treatment at five-leaf stage of foxtail millet on growth parameters, antioxidant enzymes, malondialdehyde (MDA), chlorophyll, net photosynthetic rate (P N ), chlorophyll fluorescence and P 700 parameters were studied 7 and 15 d after herbicide treatment, respectively. Results showed that Sigma Broad significantly decreased plant height, activities of superoxide dismutase (SOD), chlorophyll content, P N , PS II effective quantum yield (Y (II)), PS II electron transport rate (ETR (II)), photochemical quantum yield of PSI(Y (I)) and PS I electron transport rate ETR (I), but significantly increased MDA. Compared to herbicide treatment, BR dramatically increased plant height, activities of SOD, Y (II), ETR (II), Y (I) and ETR (I). This study showed BR pretreatment could improve the tolerance of Sigma Broad in foxtail millet through improving the activity of antioxidant enzymes, keeping electron transport smooth, and enhancing actual photochemical efficiency of PS II and PSI.

Overexpression of a Chimeric Gene, OsDST-SRDX, Improved Salt Tolerance of Perennial Ryegrass

PubMed Central

Cen, Huifang; Ye, Wenxing; Liu, Yanrong; Li, Dayong; Wang, Kexin; Zhang, Wanjun

2016-01-01

The Drought and Salt Tolerance gene (DST) encodes a C2H2 zinc finger transcription factor, which negatively regulates salt tolerance in rice (Oryza sativa). Phylogenetic analysis of six homologues of DST genes in different plant species revealed that DST genes were conserved evolutionarily. Here, the rice DST gene was linked to an SRDX domain for gene expression repression based on the Chimeric REpressor gene-Silencing Technology (CRES-T) to make a chimeric gene (OsDST-SRDX) construct and introduced into perennial ryegrass by Agrobacterium-mediated transformation. Integration and expression of the OsDST-SRDX in transgenic plants were tested by PCR and RT-PCR, respectively. Transgenic lines overexpressing the OsDST-SRDX fusion gene showed obvious phenotypic differences and clear resistance to salt-shock and to continuous salt stresses compared to non-transgenic plants. Physiological analyses including relative leaf water content, electrolyte leakage, proline content, malondialdehyde (MDA) content, H2O2 content and sodium and potassium accumulation indicated that the OsDST-SRDX fusion gene enhanced salt tolerance in transgenic perennial ryegrass by altering a wide range of physiological responses. To our best knowledge this study is the first report of utilizing Chimeric Repressor gene-Silencing Technology (CRES-T) in turfgrass and forage species for salt-tolerance improvement. PMID:27251327

Co-Expression of Monodehydroascorbate Reductase and Dehydroascorbate Reductase from Brassica rapa Effectively Confers Tolerance to Freezing-Induced Oxidative Stress

PubMed Central

Shin, Sun-Young; Kim, Myung-Hee; Kim, Yul-Ho; Park, Hyang-Mi; Yoon, Ho-Sung

2013-01-01

Plants are exposed to various environmental stresses and have therefore developed antioxidant enzymes and molecules to protect their cellular components against toxicity derived from reactive oxygen species (ROS). Ascorbate is a very important antioxidant molecule in plants, and monodehydroascorbate reductase (MDHAR; EC 1.6.5.4) and dehydroascorbate reductase (DHAR; EC 1.8.5.1) are essential to regeneration of ascorbate for maintenance of ROS scavenging ability. The MDHAR and DHAR genes from Brassica rapa were cloned, transgenic plants overexpressing either BrMDHAR and BrDHAR were established, and then, each transgenic plant was hybridized to examine the effects of co-expression of both genes conferring tolerance to freezing. Transgenic plants co-overexpressing BrMDHAR and BrDHAR showed activated expression of relative antioxidant enzymes, and enhanced levels of glutathione and phenolics under freezing condition. Then, these alteration caused by co-expression led to alleviated redox status and lipid peroxidation and consequently conferred improved tolerance against severe freezing stress compared to transgenic plants overexpressing single gene. The results of this study suggested that although each expression of BrMDHAR or BrDHAR was available to according tolerance to freezing, the simultaneous expression of two genes generated synergistic effects conferring improved tolerance more effectively even severe freezing. PMID:24170089

Cold resistance depends on acclimation and behavioral caste in a temperate ant

NASA Astrophysics Data System (ADS)

Modlmeier, Andreas P.; Pamminger, Tobias; Foitzik, Susanne; Scharf, Inon

2012-10-01

Adjusting to low temperatures is important for animals living in cold environments. We studied the chill-coma recovery time in temperate ant workers ( Temnothorax nylanderi) from colonies collected in autumn and spring in Germany. We experimentally acclimated these ant colonies to cold temperatures followed by warm temperatures. As expected, cold-acclimated workers recovered faster from freezing temperatures, but subsequent heat acclimation did not change the short recovery times observed after cold acclimation. Hence, either heat acclimation improves cold tolerance, possibly as a general response to stress, or at least it does not negate enhanced cold tolerance following cold acclimation. Colonies collected in spring showed similar cold tolerance levels to cold-acclimated colonies in the laboratory. Next, we compared the chill-coma recovery time of different worker castes and found that exterior workers recovered faster than interior workers. This difference may be related to their more frequent exposure to cold, higher activity level, or distinct physiology. Interior workers were also heavier and showed a higher gaster-to-head ratio and thorax ratio compared to exterior workers. An obvious difference between exterior and interior workers is activity level, but we found no link between activity and cold tolerance. This suggests that physiology rather than behavioral differences could cause the increased cold tolerance of exterior workers. Our study reveals the importance of acclimation for cold tolerance under natural and standardized conditions and demonstrates differences in cold tolerance and body dimensions in monomorphic behavioral castes of an ant.

Comparative functional genomics of salt stress in related model and cultivated plants identifies and overcomes limitations to translational genomics.

PubMed

Sanchez, Diego H; Pieckenstain, Fernando L; Szymanski, Jedrzey; Erban, Alexander; Bromke, Mariusz; Hannah, Matthew A; Kraemer, Ute; Kopka, Joachim; Udvardi, Michael K

2011-02-14

One of the objectives of plant translational genomics is to use knowledge and genes discovered in model species to improve crops. However, the value of translational genomics to plant breeding, especially for complex traits like abiotic stress tolerance, remains uncertain. Using comparative genomics (ionomics, transcriptomics and metabolomics) we analyzed the responses to salinity of three model and three cultivated species of the legume genus Lotus. At physiological and ionomic levels, models responded to salinity in a similar way to crop species, and changes in the concentration of shoot Cl(-) correlated well with tolerance. Metabolic changes were partially conserved, but divergence was observed amongst the genotypes. Transcriptome analysis showed that about 60% of expressed genes were responsive to salt treatment in one or more species, but less than 1% was responsive in all. Therefore, genotype-specific transcriptional and metabolic changes overshadowed conserved responses to salinity and represent an impediment to simple translational genomics. However, 'triangulation' from multiple genotypes enabled the identification of conserved and tolerant-specific responses that may provide durable tolerance across species.

Co-expression of P173S Mutant Rice EPSPS and igrA Genes Results in Higher Glyphosate Tolerance in Transgenic Rice

PubMed Central

Fartyal, Dhirendra; Agarwal, Aakrati; James, Donald; Borphukan, Bhabesh; Ram, Babu; Sheri, Vijay; Yadav, Renu; Manna, Mrinalini; Varakumar, Panditi; Achary, V. Mohan M.; Reddy, Malireddy K.

2018-01-01

Weeds and their devastating effects have been a great threat since the start of agriculture. They compete with crop plants in the field and negatively influence the crop yield quality and quantity along with survival of the plants. Glyphosate is an important broad-spectrum systemic herbicide which has been widely used to combat various weed problems since last two decades. It is very effective even at low concentrations, and possesses low environmental toxicity and soil residual activity. However, the residual concentration of glyphosate inside the plant has been of major concern as it severely affects the important metabolic pathways, and results in poor plant growth and grain yield. In this study, we compared the glyphosate tolerance efficiency of two different transgenic groups over expressing proline/173/serine (P173S) rice EPSPS glyphosate tolerant mutant gene (OsmEPSPS) alone and in combination with the glyphosate detoxifying encoding igrA gene, recently characterized from Pseudomonas. The molecular analysis of all transgenic plant lines showed a stable integration of transgenes and their active expression in foliar tissues. The physiological analysis of glyphosate treated transgenic lines at seed germination and vegetative stages showed a significant difference in glyphosate tolerance between the two transgenic groups. The transgenic plants with OsmEPSPS and igrA genes, representing dual glyphosate tolerance mechanisms, showed an improved root-shoot growth, physiology, overall phenotype and higher level of glyphosate tolerance compared to the OsmEPSPS transgenic plants. This study highlights the advantage of igrA led detoxification mechanism as a crucial component of glyphosate tolerance strategy in combination with glyphosate tolerant OsmEPSPS gene, which offered a better option to tackle in vivo glyphosate accumulation and imparted more robust glyphosate tolerance in rice transgenic plants. PMID:29487608

Co-expression of P173S Mutant Rice EPSPS and igrA Genes Results in Higher Glyphosate Tolerance in Transgenic Rice.

PubMed

Fartyal, Dhirendra; Agarwal, Aakrati; James, Donald; Borphukan, Bhabesh; Ram, Babu; Sheri, Vijay; Yadav, Renu; Manna, Mrinalini; Varakumar, Panditi; Achary, V Mohan M; Reddy, Malireddy K

2018-01-01

Weeds and their devastating effects have been a great threat since the start of agriculture. They compete with crop plants in the field and negatively influence the crop yield quality and quantity along with survival of the plants. Glyphosate is an important broad-spectrum systemic herbicide which has been widely used to combat various weed problems since last two decades. It is very effective even at low concentrations, and possesses low environmental toxicity and soil residual activity. However, the residual concentration of glyphosate inside the plant has been of major concern as it severely affects the important metabolic pathways, and results in poor plant growth and grain yield. In this study, we compared the glyphosate tolerance efficiency of two different transgenic groups over expressing proline/173/serine (P173S) rice EPSPS glyphosate tolerant mutant gene ( OsmEPSPS ) alone and in combination with the glyphosate detoxifying encoding igrA gene, recently characterized from Pseudomonas . The molecular analysis of all transgenic plant lines showed a stable integration of transgenes and their active expression in foliar tissues. The physiological analysis of glyphosate treated transgenic lines at seed germination and vegetative stages showed a significant difference in glyphosate tolerance between the two transgenic groups. The transgenic plants with OsmEPSPS and igrA genes, representing dual glyphosate tolerance mechanisms, showed an improved root-shoot growth, physiology, overall phenotype and higher level of glyphosate tolerance compared to the OsmEPSPS transgenic plants. This study highlights the advantage of igrA led detoxification mechanism as a crucial component of glyphosate tolerance strategy in combination with glyphosate tolerant OsmEPSPS gene, which offered a better option to tackle in vivo glyphosate accumulation and imparted more robust glyphosate tolerance in rice transgenic plants.

Associations between women's perceptions of domestic violence and contraceptive use in seven countries in West and Central Africa.

PubMed

Olorunsaiye, Comfort Z; Brunner Huber, Larissa; Laditka, Sarah B; Kulkarni, Shanti; Boyd, A Suzanne

2017-10-01

This study examined associations of women's attitudes toward domestic violence (DV) and contraceptive use in West and Central Africa. We used data from the Multiple Indicator Cluster Surveys for women in seven countries in West and Central Africa (2009-2011, n=80,055). We measured contraceptive use as none, traditional, or modern contraceptives. DV approval was measured as no, low, or high tolerance of wife beating. Multinomial logistic regression estimated odds of using traditional or modern methods versus none, adjusting for age, education, wealth, residence, parity, marital structure, spousal age-difference, and religion. Many women had no or low DV tolerance (41%, 44%, respectively); most used no contraception (81%). In adjusted results, women with low DV tolerance had lower odds of using traditional contraceptive methods (odds ratio, OR=0.87; 95% confidence interval, CI: 0.78-0.98) or modern methods (OR=0.86; 95% CI: 0.78-0.95) compared to women with no tolerance. Women with high DV tolerance had 28% lower odds of traditional contraceptive use (95% CI: 0.60-0.90), and 38% lower odds of modern contraceptive use (95% CI: 0.59-0.88) compared to women with no tolerance. The high prevalence of DV approval may threaten the success of programs aimed at improving women's reproductive health, including contraceptive use. Copyright © 2017 Elsevier B.V. All rights reserved.

Clinical potential of aclidinium bromide in chronic obstructive pulmonary disease.

PubMed

Jones, Paul W

2015-01-01

Three long-acting muscarinic antagonists (LAMAs) are now available in Europe, providing clinicians and patients with a choice of interventions, which is important in COPD, which is clinically a heterogeneous disease. The first LAMA, tiotropium, has been widely used over the last decade as a once-daily maintenance therapy in stable COPD to improve patients' health-related quality of life and to reduce the risk of exacerbations. Administered via the HandiHaler(®) device, it is safe and well tolerated. Another new once-daily LAMA, glycopyrronium, has also been shown to improve health status and reduce exacerbations, and is well tolerated. The subject of this review is a third LAMA, aclidinium bromide, which was approved as a twice-daily maintenance bronchodilator treatment. In the pivotal Phase III clinical trials, patients receiving aclidinium achieved significantly greater improvements in lung function, reductions in breathlessness, and improvements in health status compared with placebo, for up to 24 weeks. In continuation studies, these improvements were sustained for up to 52 weeks. Pooled data showed exacerbation frequency was significantly reduced with aclidinium versus placebo. Preclinical and pharmacological studies demonstrating low systemic bioavailability and a low propensity to induce cardiac arrhythmias were translated into a favorable tolerability profile in the clinical trial program - the adverse event profile of aclidinium was similar to placebo, with a low incidence of anticholinergic and cardiac adverse events. While additional studies are needed to evaluate its full clinical potential, aclidinium is an important part of this recent expansion of LAMA therapeutic options, providing clinicians and patients with an effective and well-tolerated COPD treatment.

Salt acclimation process: a comparison between a sensitive and a tolerant Olea europaea cultivar.

PubMed

Pandolfi, Camilla; Bazihizina, Nadia; Giordano, Cristiana; Mancuso, Stefano; Azzarello, Elisa

2017-03-01

Saline soils are highly heterogeneous in time and space, and this is a critical factor influencing plant physiology and productivity. Temporal changes in soil salinity can alter plant responses to salinity, and pre-treating plants with low NaCl concentrations has been found to substantially increase salt tolerance in different species in a process called acclimation. However, it still remains unclear whether this process is common to all plants or is only expressed in certain genotypes. We addressed this question by assessing the physiological changes to 100 mM NaCl in two contrasting olive cultivars (the salt-sensitive Leccino and the salt-tolerant Frantoio), following a 1-month acclimation period with 5 or 25 mM NaCl. The acclimation improved salt tolerance in both cultivars, but activated substantially different physiological adjustments in the tolerant and the sensitive cultivars. In the tolerant Frantoio the acclimation with 5 mM NaCl was more effective in increasing plant salt tolerance, with a 47% increase in total plant dry mass compared with non-acclimated saline plants. This enhanced biomass accumulation was associated with a 50% increase in K+ retention ability in roots. On the other hand, in the sensitive Leccino, although the acclimation process did not improve performance in terms of plant growth, pre-treatment with 5 and 25 mM NaCl substantially decreased salt-induced leaf cell ultrastructural changes, with leaf cell relatively similar to those of control plants. Taken together these results suggest that in the tolerant cultivar the acclimation took place primarily in the root tissues, while in the sensitive they occurred mainly at the shoot level. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A banana aquaporin gene, MaPIP1;1, is involved in tolerance to drought and salt stresses

PubMed Central

2014-01-01

Background Aquaporin (AQP) proteins function in transporting water and other small molecules through the biological membranes, which is crucial for plants to survive in drought or salt stress conditions. However, the precise role of AQPs in drought and salt stresses is not completely understood in plants. Results In this study, we have identified a PIP1 subfamily AQP (MaPIP1;1) gene from banana and characterized it by overexpression in transgenic Arabidopsis plants. Transient expression of MaPIP1;1-GFP fusion protein indicated its localization at plasma membrane. The expression of MaPIP1;1 was induced by NaCl and water deficient treatment. Overexpression of MaPIP1;1 in Arabidopsis resulted in an increased primary root elongation, root hair numbers and survival rates compared to WT under salt or drought conditions. Physiological indices demonstrated that the increased salt tolerance conferred by MaPIP1;1 is related to reduced membrane injury and high cytosolic K+/Na+ ratio. Additionally, the improved drought tolerance conferred by MaPIP1;1 is associated with decreased membrane injury and improved osmotic adjustment. Finally, reduced expression of ABA-responsive genes in MaPIP1;1-overexpressing plants reflects their improved physiological status. Conclusions Our results demonstrated that heterologous expression of banana MaPIP1;1 in Arabidopsis confers salt and drought stress tolerances by reducing membrane injury, improving ion distribution and maintaining osmotic balance. PMID:24606771

Children's and Parents' Ability to Tolerate Child Distress: Impact on Cognitive Behavioral Therapy for Pediatric Obsessive Compulsive Disorder.

PubMed

Selles, Robert R; Franklin, Martin; Sapyta, Jeffrey; Compton, Scott N; Tommet, Doug; Jones, Richard N; Garcia, Abbe; Freeman, Jennifer

2018-04-01

The present study explored the concept of tolerance for child distress in 46 children (ages 5-8), along with their mothers and fathers, who received family-based CBT for OCD. The study sought to describe baseline tolerance, changes in tolerance with treatment, and the predictive impact of tolerance on symptom improvement. Tolerance was rated by clinicians on a single item and the CY-BOCS was used to measure OCD severity. Descriptive results suggested that all participants had some difficulty tolerating the child's distress at baseline while paired t tests indicated large improvements were made over treatment (d = 1.2-2.0). Fathers' initial tolerance was significantly related to symptom improvement in a multivariate regression as were fathers' and children's changes in distress tolerance over the course of treatment. Overall, results provide support for examining tolerance of child distress including its predictive impact and potential as a supplemental intervention target.

Combining inhibitor tolerance and D-xylose fermentation in industrial Saccharomyces cerevisiae for efficient lignocellulose-based bioethanol production.

PubMed

Demeke, Mekonnen M; Dumortier, Françoise; Li, Yingying; Broeckx, Tom; Foulquié-Moreno, María R; Thevelein, Johan M

2013-08-26

In addition to efficient pentose utilization, high inhibitor tolerance is a key trait required in any organism used for economically viable industrial bioethanol production with lignocellulose biomass. Although recent work has succeeded in establishing efficient xylose fermentation in robust industrial Saccharomyces cerevisiae strains, the resulting strains still lacked sufficient inhibitor tolerance for efficient sugar fermentation in lignocellulose hydrolysates. The aim of the present work was to combine high xylose fermentation activity and high inhibitor tolerance in a single industrial yeast strain. We have screened 580 yeast strains for high inhibitor tolerance using undetoxified acid-pretreated spruce hydrolysate and identified a triploid industrial baker's yeast strain as having the highest inhibitor tolerance. From this strain, a mating competent diploid segregant with even higher inhibitor tolerance was obtained. It was crossed with the recently developed D-xylose fermenting diploid industrial strain GS1.11-26, with the Ethanol Red genetic background. Screening of 819 diploid segregants from the tetraploid hybrid resulted in two strains, GSF335 and GSF767, combining high inhibitor tolerance and efficient xylose fermentation. In a parallel approach, meiotic recombination of GS1.11-26 with a haploid segregant of Ethanol Red and screening of 104 segregants resulted in a similar inhibitor tolerant diploid strain, GSE16. The three superior strains exhibited significantly improved tolerance to inhibitors in spruce hydrolysate, higher glucose consumption rates, higher aerobic growth rates and higher maximal ethanol accumulation capacity in very-high gravity fermentation, compared to GS1.11-26. In complex medium, the D-xylose utilization rate by the three superior strains ranged from 0.36 to 0.67 g/g DW/h, which was lower than that of GS1.11-26 (1.10 g/g DW/h). On the other hand, in batch fermentation of undetoxified acid-pretreated spruce hydrolysate, the three superior strains showed comparable D-xylose utilization rates as GS1.11-26, probably because of their higher inhibitor tolerance. They produced up to 23% more ethanol compared to Ethanol Red. We have successfully constructed three superior industrial S. cerevisiae strains that combine efficient D-xylose utilization with high inhibitor tolerance. Since the background strain Ethanol Red has a proven record of successful industrial application, the three new superior strains have strong potential for direct application in industrial bioethanol production.

Combining inhibitor tolerance and D-xylose fermentation in industrial Saccharomyces cerevisiae for efficient lignocellulose-based bioethanol production

PubMed Central

2013-01-01

Background In addition to efficient pentose utilization, high inhibitor tolerance is a key trait required in any organism used for economically viable industrial bioethanol production with lignocellulose biomass. Although recent work has succeeded in establishing efficient xylose fermentation in robust industrial Saccharomyces cerevisiae strains, the resulting strains still lacked sufficient inhibitor tolerance for efficient sugar fermentation in lignocellulose hydrolysates. The aim of the present work was to combine high xylose fermentation activity and high inhibitor tolerance in a single industrial yeast strain. Results We have screened 580 yeast strains for high inhibitor tolerance using undetoxified acid-pretreated spruce hydrolysate and identified a triploid industrial baker’s yeast strain as having the highest inhibitor tolerance. From this strain, a mating competent diploid segregant with even higher inhibitor tolerance was obtained. It was crossed with the recently developed D-xylose fermenting diploid industrial strain GS1.11-26, with the Ethanol Red genetic background. Screening of 819 diploid segregants from the tetraploid hybrid resulted in two strains, GSF335 and GSF767, combining high inhibitor tolerance and efficient xylose fermentation. In a parallel approach, meiotic recombination of GS1.11-26 with a haploid segregant of Ethanol Red and screening of 104 segregants resulted in a similar inhibitor tolerant diploid strain, GSE16. The three superior strains exhibited significantly improved tolerance to inhibitors in spruce hydrolysate, higher glucose consumption rates, higher aerobic growth rates and higher maximal ethanol accumulation capacity in very-high gravity fermentation, compared to GS1.11-26. In complex medium, the D-xylose utilization rate by the three superior strains ranged from 0.36 to 0.67 g/g DW/h, which was lower than that of GS1.11-26 (1.10 g/g DW/h). On the other hand, in batch fermentation of undetoxified acid-pretreated spruce hydrolysate, the three superior strains showed comparable D-xylose utilization rates as GS1.11-26, probably because of their higher inhibitor tolerance. They produced up to 23% more ethanol compared to Ethanol Red. Conclusions We have successfully constructed three superior industrial S. cerevisiae strains that combine efficient D-xylose utilization with high inhibitor tolerance. Since the background strain Ethanol Red has a proven record of successful industrial application, the three new superior strains have strong potential for direct application in industrial bioethanol production. PMID:23971950

Efficacy, safety, and tolerance of the non-ergoline dopamine agonist pramipexole in the treatment of advanced Parkinson's disease: a double blind, placebo controlled, randomised, multicentre study.

PubMed

Pinter, M M; Pogarell, O; Oertel, W H

1999-04-01

Pramipexole, a non-ergot dopamine D2/D3 receptor agonist, was investigated as an add on drug in advanced parkinsonian patients with motor fluctuations to assess efficacy, safety, and tolerance. Seventy eight patients of either sex with advanced Parkinson's disease and treatment complications such as motor fluctuations were enrolled into a double blind, placebo controlled, randomised, multicentre study (phase II) and assigned to add on treatment with pramipexole (n=34) versus placebo (n=44) to a previously stabilised antiparkinsonian medication (7 week dose titration interval, 4 week maintenance period). The primary end point of efficacy was the change from baseline in the total score of the unified Parkinson's disease rating scale (UPDRS) in the on "period" (2 hours after intake of study medication). Safety and tolerability were assessed on the basis of adverse events, vital signs, laboratory measurements, and ECG recordings. There was a significant improvement of the pramipexole group in UPDRS total scores, subscores part II, III (activities of daily living and motor examination), and IV (complications of therapy). Mean UPDRS total score decreased by 37.3% under pramipexole compared with 12.2% under placebo (p<0.001). Patients under pramipexole reported an overall reduction in "off" periods of 12%--resulting in 1.7 more hours "on" time a day--compared with an increase in "off" periods of 2% under placebo. There were no unexpected safety results. The adverse event profile disclosed a high tolerability. The most important adverse events under pramipexole were fatigue, dyskinesia, and vivid dreams. Pramipexole administration is an efficacious and well tolerated add on therapy in patients with advanced Parkinson's disease with an improvement in activities of daily living, motor function, and treatment associated complications.

Efficacy, safety and tolerability of rasagiline as adjunctive therapy in elderly patients with Parkinson's disease.

PubMed

Tolosa, E; Stern, M B

2012-02-01

Rasagiline, an MAO-B inhibitor, is indicated for the treatment of Parkinson's disease (PD). In this post hoc analysis, the efficacy, safety and tolerability of rasagiline as an adjunct to levodopa were compared with placebo in elderly (≥70 years) and younger (<70 years) patients with PD. Data were pooled from the Parkinson's Rasagiline: Efficacy and Safety on the Treatment of 'OFF' and Lasting effect in Adjunct therapy with Rasagiline Given Once daily randomized, double-blind, placebo-controlled trials with the primary efficacy end-point being the reduction from baseline in daily OFF time. Secondary efficacy end-points included scores for Clinical Global Improvement (CGI)-Examiner during ON time, Unified Parkinson's Disease Rating Scale (UPDRS)-ADL during OFF time, UPDRS-Motor during ON time and total daily ON time with and without troublesome dyskinesia. Tolerability was evaluated from adverse events (AEs) in the two age groups. Rasagiline decreased daily OFF time versus placebo (P<0.01) and improved CGI-Examiner score (P=0.001) and UPDRS-Motor ON score (P<0.05). Changes in UPDRS-ADL OFF score and total daily ON time without dyskinesia also favoured rasagiline but were not significant. Between-group comparisons (≥70 vs. <70 years) showed that efficacy was unaffected by age for all end-points (P>0.1), and rasagiline was well tolerated amongst both groups of patients with a comparable incidence of total and dopaminergic AEs (P>0.1). Adjunct rasagiline is efficacious and well tolerated in elderly non-demented patients (≥70 years) with moderate to advanced PD. Confirmation of the efficacy and safety of rasagiline in the elderly patient subgroup is especially relevant because of the increasing number of elderly patients with PD. © 2011 The Author(s). European Journal of Neurology © 2011 EFNS.

Improved enteral tolerance following step procedure: systematic literature review and meta-analysis.

PubMed

Fernandes, Melissa A; Usatin, Danielle; Allen, Isabel E; Rhee, Sue; Vu, Lan

2016-10-01

Surgical management of children with short bowel syndrome (SBS) changed with the introduction of the serial transverse enteroplasty procedure (STEP). We conducted a systematic review and meta-analysis using MEDLINE and SCOPUS to determine if children with SBS had improved enteral tolerance following STEP. Studies were included if information about a child's pre- and post-STEP enteral tolerance was provided. A random effects meta-analysis provided a summary estimate of the proportion of children with enteral tolerance increase following STEP. From 766 abstracts, seven case series involving 86 children were included. Mean percent tolerance of enteral nutrition improved from 35.1 to 69.5. Sixteen children had no enteral improvement following STEP. A summary estimate showed that 87 % (95 % CI 77-95 %) of children who underwent STEP had an increase in enteral tolerance. Compilation of the literature supports the belief that SBS subjects' enteral tolerance improves following STEP. Enteral nutritional tolerance is a measure of efficacy of STEP and should be presented as a primary or secondary outcome. By standardizing data collection on children undergoing STEP procedure, better determination of nutritional benefit from STEP can be ascertained.

Over-Expression of Arabidopsis EDT1 Gene Confers Drought Tolerance in Alfalfa (Medicago sativa L.)

PubMed Central

Zheng, Guangshun; Fan, Cunying; Di, Shaokang; Wang, Xuemin; Xiang, Chengbin; Pang, Yongzhen

2017-01-01

Alfalfa (Medicago sativa L.) is an important legume forage crop with great economic value. However, as the growth of alfalfa is seriously affected by an inadequate supply of water, drought is probably the major abiotic environmental factor that most severely affects alfalfa production worldwide. In an effort to enhance alfalfa drought tolerance, we transformed the Arabidopsis Enhanced Drought Tolerance 1 (AtEDT1) gene into alfalfa via Agrobacterium-mediated transformation. Compared with wild type plants, drought stress treatment resulted in higher survival rates and biomass, but reduced water loss rates in the transgenic plants. Furthermore, transgenic alfalfa plants had increased stomatal size, but reduced stomatal density, and these stomatal changes contributed greatly to reduced water loss from leaves. Importantly, transgenic alfalfa plants exhibited larger root systems with larger root lengths, root weight, and root diameters than wild type plants. The transgenic alfalfa plants had reduced membrane permeability and malondialdehyde content, but higher soluble sugar and proline content, higher superoxide dismutase activity, higher chlorophyll content, enhanced expression of drought-responsive genes, as compared with wild type plants. Notably, transgenic alfalfa plants grew better in a 2-year field trial and showed enhanced growth performance with increased biomass yield. All of our morphological, physiological, and molecular analyses demonstrated that the ectopic expression of AtEDT1 improved growth and enhanced drought tolerance in alfalfa. Our study provides alfalfa germplasm for use in forage improvement programs, and may help to increase alfalfa production in arid lands. PMID:29326737

Over-Expression of Arabidopsis EDT1 Gene Confers Drought Tolerance in Alfalfa (Medicago sativa L.).

PubMed

Zheng, Guangshun; Fan, Cunying; Di, Shaokang; Wang, Xuemin; Xiang, Chengbin; Pang, Yongzhen

2017-01-01

Alfalfa ( Medicago sativa L.) is an important legume forage crop with great economic value. However, as the growth of alfalfa is seriously affected by an inadequate supply of water, drought is probably the major abiotic environmental factor that most severely affects alfalfa production worldwide. In an effort to enhance alfalfa drought tolerance, we transformed the Arabidopsis Enhanced Drought Tolerance 1 ( AtEDT1 ) gene into alfalfa via Agrobacterium -mediated transformation. Compared with wild type plants, drought stress treatment resulted in higher survival rates and biomass, but reduced water loss rates in the transgenic plants. Furthermore, transgenic alfalfa plants had increased stomatal size, but reduced stomatal density, and these stomatal changes contributed greatly to reduced water loss from leaves. Importantly, transgenic alfalfa plants exhibited larger root systems with larger root lengths, root weight, and root diameters than wild type plants. The transgenic alfalfa plants had reduced membrane permeability and malondialdehyde content, but higher soluble sugar and proline content, higher superoxide dismutase activity, higher chlorophyll content, enhanced expression of drought-responsive genes, as compared with wild type plants. Notably, transgenic alfalfa plants grew better in a 2-year field trial and showed enhanced growth performance with increased biomass yield. All of our morphological, physiological, and molecular analyses demonstrated that the ectopic expression of AtEDT1 improved growth and enhanced drought tolerance in alfalfa. Our study provides alfalfa germplasm for use in forage improvement programs, and may help to increase alfalfa production in arid lands.

Overexpression of the TaSHN1 transcription factor in bread wheat leads to leaf surface modifications, improved drought tolerance and no yield penalty under controlled growth conditions.

PubMed

Bi, Huihui; Shi, Jianxin; Kovalchuk, Natalia; Luang, Sukanya; Bazanova, Natalia; Chirkova, Larissa; Zhang, Dabing; Shavrukov, Yuri; Stepanenko, Anton; Tricker, Penny; Langridge, Peter; Hrmova, Maria; Lopato, Sergiy; Borisjuk, Nikolai

2018-05-14

Transcription factors regulate multiple networks, mediating the responses of organisms to stresses, including drought. Here we investigated the role of the wheat transcription factor TaSHN1 in crop growth and drought tolerance. TaSHN1, isolated from bread wheat, was characterised for molecular interactions and functionality. The overexpression of TaSHN1 in wheat was followed by the evaluation of T 2 and T 3 transgenic lines for drought tolerance, growth and yield components. Leaf surface changes were analysed by light microscopy, SEM, TEM and GC-MS/GC-FID. TaSHN1 behaves as a transcriptional activator in a yeast transactivation assay and binds stress-related DNA cis-elements, determinants of which were revealed using 3D molecular modelling. The overexpression of TaSHN1 in transgenic wheat did not result in a yield penalty under the controlled plant growth conditions of a glasshouse. Transgenic lines had significantly lower stomatal density and leaf water loss, and exhibited improved recovery after severe drought, compared to control plants. The comparative analysis of cuticular waxes revealed an increased accumulation of alkanes in leaves of transgenic lines. Our data demonstrate that TaSHN1 may operate as a positive modulator of drought stress tolerance. Positive attributes could be mediated through an enhanced accumulation of alkanes and reduced stomatal density. This article is protected by copyright. All rights reserved.

Functional Genomics of Drought Tolerance in Bioenergy Crops

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yin, Hengfu; Chen, Rick; Yang, Jun

2014-01-01

With the predicted trends in climate change, drought will increasingly impose a grand challenge to biomass production. Most of the bioenergy crops have some degree of drought susceptibility with low water-use efficiency (WUE). It is imperative to improve drought tolerance and WUE in bioenergy crops for sustainable biomass production in arid and semi-arid regions with minimal water input. Genetics and functional genomics can play a critical role in generating knowledge to inform and aid genetic improvement of drought tolerance in bioenergy crops. The molecular aspect of drought response has been extensively investigated in model plants like Arabidopsis, yet our understandingmore » of the molecular mechanisms underlying drought tolerance in bioenergy crops are limited. Crops exhibit various responses to drought stress depending on species and genotype. A rational strategy for studying drought tolerance in bioenergy crops is to translate the knowledge from model plants and pinpoint the unique features associated with individual species and genotypes. In this review, we summarize the general knowledge about drought responsive pathways in plants, with a focus on the identification of commonality and specialty in drought responsive mechanisms among different species and/or genotypes. We describe the genomic resources developed for bioenergy crops and discuss genetic and epigenetic regulation of drought responses. We also examine comparative and evolutionary genomics to leverage the ever-increasing genomics resources and provide new insights beyond what has been known from studies on individual species. Finally, we outline future exploration of drought tolerance using the emerging new technologies.« less

Efficacy and tolerability of preservative-free eye drops containing a fixed combination of dorzolamide and timolol in glaucoma patients.

PubMed

Renieri, Giulia; Führer, Katrin; Scheithe, Karl; Lorenz, Katrin; Pfeiffer, Norbert; Thieme, Hagen

2010-12-01

To evaluate the efficacy and tolerability of preservative-free eye drops (dorzolamide/timolol) in routine management of preservative-sensitive glaucoma patients. Data from 2,298 glaucoma patients requiring intraocular pressure (IOP) reduction and suffering from intolerance to benzalkonium chloride or active agents of previously used eye drops were valid for baseline and safety analysis in this prospective, open, noncomparative, multicenter, noninterventional study. Patients were treated with preservative-free dorzolamide/timolol eye drops for 12 weeks. Main efficacy endpoint was IOP reduction after 12 weeks of treatment. Two thousand forty-nine patients were considered for efficacy analysis. Tolerability was assessed by evaluating adverse drug reactions. Mean baseline IOP was 20.8 mmHg. Baseline IOP was reduced to 16.7 mmHg after 12 weeks of treatment corresponding to a mean absolute (percent) change of -4.1 mmHg (-17.3%). The proportion of patients with IOP ≤21 mmHg increased from 59.9% at baseline to 94.6% after 12 weeks. The most frequently reported ocular adverse drug reactions were burning eyes (2.4%) and hyperemia (0.9%). Local tolerability improved in 79.3% of patients compared to their previous glaucoma therapy. This observational study confirms the IOP lowering effect of preservative-free eye drops containing the fixed combination of dorzolamide/timolol in a large patient's population. The drug was well tolerated and improved the local tolerability in the vast majority of patients.

Privacy-Assured Aggregation Protocol for Smart Metering: A Proactive Fault-Tolerant Approach [Proactive Fault-Tolerant Aggregation Protocol for Privacy-Assured Smart Metering

DOE PAGES

Won, Jongho; Ma, Chris Y. T.; Yau, David K. Y.; ...

2016-06-01

Smart meters are integral to demand response in emerging smart grids, by reporting the electricity consumption of users to serve application needs. But reporting real-time usage information for individual households raises privacy concerns. Existing techniques to guarantee differential privacy (DP) of smart meter users either are not fault tolerant or achieve (possibly partial) fault tolerance at high communication overheads. In this paper, we propose a fault-tolerant protocol for smart metering that can handle general communication failures while ensuring DP with significantly improved efficiency and lower errors compared with the state of the art. Our protocol handles fail-stop faults proactively bymore » using a novel design of future ciphertexts, and distributes trust among the smart meters by sharing secret keys among them. We prove the DP properties of our protocol and analyze its advantages in fault tolerance, accuracy, and communication efficiency relative to competing techniques. We illustrate our analysis by simulations driven by real-world traces of electricity consumption.« less

Privacy-Assured Aggregation Protocol for Smart Metering: A Proactive Fault-Tolerant Approach [Proactive Fault-Tolerant Aggregation Protocol for Privacy-Assured Smart Metering

DOE Office of Scientific and Technical Information (OSTI.GOV)

Won, Jongho; Ma, Chris Y. T.; Yau, David K. Y.

Smart meters are integral to demand response in emerging smart grids, by reporting the electricity consumption of users to serve application needs. But reporting real-time usage information for individual households raises privacy concerns. Existing techniques to guarantee differential privacy (DP) of smart meter users either are not fault tolerant or achieve (possibly partial) fault tolerance at high communication overheads. In this paper, we propose a fault-tolerant protocol for smart metering that can handle general communication failures while ensuring DP with significantly improved efficiency and lower errors compared with the state of the art. Our protocol handles fail-stop faults proactively bymore » using a novel design of future ciphertexts, and distributes trust among the smart meters by sharing secret keys among them. We prove the DP properties of our protocol and analyze its advantages in fault tolerance, accuracy, and communication efficiency relative to competing techniques. We illustrate our analysis by simulations driven by real-world traces of electricity consumption.« less

An Exploratory Trial of Transdermal Nicotine for Aggression and Irritability in Adults with Autism Spectrum Disorder.

PubMed

Lewis, Alan S; van Schalkwyk, Gerrit Ian; Lopez, Mayra Ortiz; Volkmar, Fred R; Picciotto, Marina R; Sukhodolsky, Denis G

2018-03-13

Nicotinic acetylcholine receptors (nAChRs), particularly the α7 nAChR, are implicated in the pathophysiology of both autism spectrum disorder (ASD) and aggressive behavior. We explored the feasibility, tolerability, and preliminary efficacy of targeting nAChRs using transdermal nicotine to reduce aggressive symptoms in adults with ASD. Eight subjects were randomized in a double-blind crossover trial of 7 mg transdermal nicotine or placebo, each for 1 week. All participants tolerated nicotine treatment well. Five subjects contributed data to the primary outcome, Aberrant Behavior Checklist-Irritability (ABC-I) subscale change from baseline, which was improved by nicotine compared to placebo. Sleep ratings were also improved by nicotine and correlated with ABC-I improvement. These findings support further investigation of nAChR agonists for aggression and sleep in ASD.

Combination of the sodium-glucose cotransporter-2 inhibitor empagliflozin with orlistat or sibutramine further improves the body-weight reduction and glucose homeostasis of obese rats fed a cafeteria diet.

PubMed

Vickers, Steven P; Cheetham, Sharon C; Headland, Katie R; Dickinson, Keith; Grempler, Rolf; Mayoux, Eric; Mark, Michael; Klein, Thomas

2014-01-01

The present study assessed the potential of the sodium glucose-linked transporter (SGLT)-2 inhibitor empagliflozin to decrease body weight when administered alone or in combination with the clinically effective weight-loss agents orlistat and sibutramine in obese rats fed a cafeteria diet. Female Wistar rats were exposed to a cafeteria diet to induce obesity. Empagliflozin was dosed once daily (10, 30, and 60 mg/kg) for 28 days. Combination studies were subsequently performed using a submaximal empagliflozin dose (10 mg/kg) with either sibutramine or orlistat. Body weight, food, and water intake were recorded daily. The effect of drug treatment on glucose tolerance, relevant plasma parameters, and carcass composition was determined. Empagliflozin dose-dependently reduced body weight, plasma leptin, and body fat though increased urinary glucose excretion. The combination of empagliflozin and orlistat significantly reduced body weight compared to animals treated with either drug alone, and significantly improved glucose tolerance, plasma insulin, and leptin compared to vehicle-treated controls. The effect of sibutramine to improve glycemic control in an oral glucose-tolerance test was also significantly increased, with empagliflozin and combination treatment leading to a reduction in carcass fat greater than that observed with either drug alone. These data demonstrate that empagliflozin reduces body weight in cafeteria-fed obese rats. In combination studies, empagliflozin further improved the body-weight or body-fat loss of animals in comparison to orlistat or sibutramine alone. Such studies may indicate improved strategies for the treatment of obese patients with prediabetes or type 2 diabetes.

Metabolic Effects of Acibenzolar-S-Methyl for Improving Heat or Drought Stress in Creeping Bentgrass

PubMed Central

Jespersen, David; Yu, Jingjin; Huang, Bingru

2017-01-01

Acibenzolar-S-methyl (ASM) is a synthetic functional analog of salicylic acid which can induce systemic acquired resistance in plants, but its effects on abiotic stress tolerance is not well known. The objectives of this study were to examine effects of acibenzolar-S-methyl on heat or drought tolerance in creeping bentgrass (Agrostis stolonifera) and to determine major ASM-responsive metabolites and proteins associated with enhanced abiotic stress tolerance. Creeping bentgrass plants (cv. ‘Penncross’) were foliarly sprayed with ASM and were exposed to non-stress (20/15°C day/night), heat stress (35/30°C), or drought conditions (by withholding irrigation) in controlled-environment growth chambers. Exogenous ASM treatment resulted in improved heat or drought tolerance, as demonstrated by higher overall turf quality, relative water content, and chlorophyll content compared to the untreated control. Western blotting revealed that ASM application resulted in up-regulation of ATP synthase, HSP-20, PR-3, and Rubisco in plants exposed to heat stress, and greater accumulation of dehydrin in plants exposed to drought stress. Metabolite profiling identified a number of amino acids, organic acids, and sugars which were differentially accumulated between ASM treated and untreated plants under heat or drought stress, including aspartic acid, glycine, citric acid, malic acid, and the sugars glucose, and fructose. Our results suggested that ASM was effective in improving heat or drought tolerance in creeping bentgrass, mainly through enhancing protein synthesis and metabolite accumulation involved in osmotic adjustment, energy metabolism, and stress signaling. PMID:28744300

Angelica dahurica Extracts Improve Glucose Tolerance through the Activation of GPR119

PubMed Central

Kim, Mi-Hwi; Choung, Jin-Seung; Oh, Yoon-Sin; Moon, Hong-Sub; Jun, Hee-Sook

2016-01-01

G protein-coupled receptor (GPR) 119 is expressed in pancreatic β-cells and intestinal L cells, and is involved in glucose-stimulated insulin secretion and glucagon-like peptide-1 (GLP-1) release, respectively. Therefore, the development of GPR119 agonists is a potential treatment for type 2 diabetes. We screened 1500 natural plant extracts for GPR119 agonistic actions and investigated the most promising extract, that from Angelica dahurica (AD), for hypoglycemic actions in vitro and in vivo. Human GPR119 activation was measured in GeneBLAzer T-Rex GPR119-CRE-bla CHO-K1 cells; intracellular cAMP levels and insulin secretion were measured in INS-1 cells; and GLP-1 release was measured in GLUTag cells. Glucose tolerance tests and serum plasma insulin levels were measured in normal C57BL6 mice and diabetic db/db mice. AD extract-treated cells showed significant increases in GPR119 activation, intracellular cAMP levels, GLP-1 levels and glucose-stimulated insulin secretion as compared with controls. In normal mice, a single treatment with AD extract improved glucose tolerance and increased insulin secretion. Treatment with multiple doses of AD extract or n-hexane fraction improved glucose tolerance in diabetic db/db mice. Imperatorin, phellopterin and isoimperatorin were identified in the active fraction of AD extract. Among these, phellopterin activated GPR119 and increased active GLP-1 and insulin secretion in vitro and enhanced glucose tolerance in normal and db/db mice. We suggest that phellopterin might have a therapeutic potential for the treatment of type 2 diabetes. PMID:27391814

The Wheat NAC Transcription Factor TaNAC2L Is Regulated at the Transcriptional and Post-Translational Levels and Promotes Heat Stress Tolerance in Transgenic Arabidopsis.

PubMed

Guo, Weiwei; Zhang, Jinxia; Zhang, Ning; Xin, Mingming; Peng, Huiru; Hu, Zhaorong; Ni, Zhongfu; Du, Jinkun

2015-01-01

Heat stress poses a serious threat to global crop production. In efforts that aim to mitigate the adverse effects of heat stress on crops, a variety of genetic tools are being used to develop plants with improved thermotolerance. The characterization of important regulators of heat stress tolerance provides essential information for this aim. In this study, we examine the wheat (Triticum aestivum) NAC transcription factor gene TaNAC2L. High temperature induced TaNAC2L expression in wheat and overexpression of TaNAC2L in Arabidopsis thaliana enhanced acquired heat tolerance without causing obvious alterations in phenotype compared with wild type under normal conditions. TaNAC2L overexpression also activated the expression of heat-related genes in the transgenic Arabidopsis plants, suggesting that TaNAC2L may improve heat tolerance by regulating the expression of stress-responsive genes. Notably, TaNAC2L is also regulated at the post-translational level and might be degraded via a proteasome-mediated pathway. Thus, this wheat transcription factor may have potential uses in enhancing thermotolerance in crops.

Risk intelligence: making profit from uncertainty in data processing system.

PubMed

Zheng, Si; Liao, Xiangke; Liu, Xiaodong

2014-01-01

In extreme scale data processing systems, fault tolerance is an essential and indispensable part. Proactive fault tolerance scheme (such as the speculative execution in MapReduce framework) is introduced to dramatically improve the response time of job executions when the failure becomes a norm rather than an exception. Efficient proactive fault tolerance schemes require precise knowledge on the task executions, which has been an open challenge for decades. To well address the issue, in this paper we design and implement RiskI, a profile-based prediction algorithm in conjunction with a riskaware task assignment algorithm, to accelerate task executions, taking the uncertainty nature of tasks into account. Our design demonstrates that the nature uncertainty brings not only great challenges, but also new opportunities. With a careful design, we can benefit from such uncertainties. We implement the idea in Hadoop 0.21.0 systems and the experimental results show that, compared with the traditional LATE algorithm, the response time can be improved by 46% with the same system throughput.

Efficacy and Tolerability of Lacosamide in the Treatment of Children With Refractory Generalized Epilepsy.

PubMed

Miskin, Chandrabhaga; Khurana, Divya S; Valencia, Ignacio; Legido, Agustin; Hasbani, Daphne M; Carvalho, Karen S

2016-06-01

Lacosamide is FDA-approved in patients 17 years or older with partial-onset epilepsy. We evaluated the efficacy and tolerability of lacosamide in children with refractory generalized epilepsy. We retrospectively reviewed records of 21 children with refractory generalized epilepsy treated with lacosamide in our institution from 2009-2013 divided into 2 subgroups- I, Lennox-Gastaut Syndrome, and II, other generalized epilepsies. Efficacy was defined as seizure freedom or ≥50% seizure reduction. Descriptive data analysis including seizure freedom was compared using c(2) analysis. There were eleven females and ten males with a mean age, of 11.9 years. Five patients became seizure free, nine had ≥50% seizure reduction, and seven had no response. Group I: seven had ≥50% improvement, one did not respond. Group II: five became seizure free, two had ≥50% improvement, five had no response. Lacosamide is effective and well tolerated in children with refractory generalized epilepsy particularly patients with Lennox-Gastaut Syndrome. © The Author(s) 2016.

Recent progress in NASA Langley Research Center textile reinforced composites program

NASA Technical Reports Server (NTRS)

Dexter, H. Benson; Harris, Charles E.; Johnston, Norman J.

1992-01-01

Research was conducted to explore the benefits of textile reinforced composites for transport aircraft primary structures. The objective is to develop and demonstrate the potential of affordable textile reinforced composite materials to meet design properties and damage tolerance requirements of advanced aircraft structural concepts. Some program elements include development of textile preforms, processing science, mechanics of materials, experimental characterization of materials, and development and evaluation of textile reinforced composite structural elements and subcomponents. Textile 3-D weaving, 3-D braiding, and knitting and/or stitching are being compared with conventional laminated tape processes for improved damage tolerance. Through-the-thickness reinforcements offer significant damage tolerance improvements. However, these gains must be weighted against potential loss in in-plane properties such as strength and stiffness. Analytical trade studies are underway to establish design guidelines for the application of textile material forms to meet specific loading requirements. Fabrication and testing of large structural parts are required to establish the potential of textile reinforced composite materials.

Efficacy and tolerability of itopride hydrochloride in patients with non-ulcer dyspepsia.

PubMed

Shenoy, K T; Veenasree; Leena, K B

2003-06-01

To document the clinical efficacy and tolerability of itopride hydrochloride in patients with non-ulcer dyspepsia an open-label, non-comparative study, was undertaken at the Medical College, Thiruvananthapuram, among patients with endoscopically confirmed diagnosis of non-ulcer dyspepsia or chronic gastritis. Itopride hydrochloride 50 mg (1 tablet) thrice a day for 2 weeks was administered among them. Relief of symptoms at the end of two weeks treatment, assessed as marked/complete, moderate, slight, none or worse; QT interval on ECG; adverse events; haemogram; serum chemistry for hepatic and renal functions. None had QT prolongation on ECG. At the end of 2 weeks' treatment, moderate to complete relief of symptoms was reported by 22 patients (73%), whereas 5 (17%) reproted slight improvement, and 3 (10%) reported no improvement. Clinical tolerability was excellent in 28 patients (93%) and good in 2 (7%). None of the patients had any prolongation of QT on ECG, nor did any patient show any abnormality in haemogram or serum chemistry during the treatment.

Risk Intelligence: Making Profit from Uncertainty in Data Processing System

PubMed Central

Liao, Xiangke; Liu, Xiaodong

2014-01-01

In extreme scale data processing systems, fault tolerance is an essential and indispensable part. Proactive fault tolerance scheme (such as the speculative execution in MapReduce framework) is introduced to dramatically improve the response time of job executions when the failure becomes a norm rather than an exception. Efficient proactive fault tolerance schemes require precise knowledge on the task executions, which has been an open challenge for decades. To well address the issue, in this paper we design and implement RiskI, a profile-based prediction algorithm in conjunction with a riskaware task assignment algorithm, to accelerate task executions, taking the uncertainty nature of tasks into account. Our design demonstrates that the nature uncertainty brings not only great challenges, but also new opportunities. With a careful design, we can benefit from such uncertainties. We implement the idea in Hadoop 0.21.0 systems and the experimental results show that, compared with the traditional LATE algorithm, the response time can be improved by 46% with the same system throughput. PMID:24883392

Estimation of Subjective Mental Work Load Level with Heart Rate Variability by Tolerance to Driver's Mental Load

NASA Astrophysics Data System (ADS)

Yokoi, Toshiyuki; Itoh, Michimasa; Oguri, Koji

Most of the traffic accidents have been caused by inappropriate driver's mental state. Therefore, driver monitoring is one of the most important challenges to prevent traffic accidents. Some studies for evaluating the driver's mental state while driving have been reported; however driver's mental state should be estimated in real-time in the future. This paper proposes a way to estimate quantitatively driver's mental workload using heart rate variability. It is assumed that the tolerance to driver's mental workload is different depending on the individual. Therefore, we classify people based on their individual tolerance to mental workload. Our estimation method is multiple linear regression analysis, and we compare it to NASA-TLX which is used as the evaluation method of subjective mental workload. As a result, the coefficient of correlation improved from 0.83 to 0.91, and the standard deviation of error also improved. Therefore, our proposed method demonstrated the possibility to estimate mental workload.

Variation of glucose tolerance in adult patients with cystic fibrosis: What is the potential contribution of insulin sensitivity?

PubMed

Boudreau, Valérie; Coriati, Adèle; Hammana, Imane; Ziai, Sophie; Desjardins, Katherine; Berthiaume, Yves; Rabasa-Lhoret, Rémi

2016-11-01

Reduced insulin secretion is a key factor to explain high prevalence of glucose intolerance in patients with cystic fibrosis (CF). However, the role of insulin sensitivity remains unclear. The aim of this study is to investigate the association of insulin secretion and sensitivity with the evolution of glucose tolerance. A total of 152 patients without known diabetes from the Montreal CF cohort underwent two 2-h oral glucose tolerance tests (OGTT) at baseline and again after 21.2±5.5months. Pulmonary function and anthropometric measurements were also collected at each visit. At both visits, based on their OGTT results, patients were categorized in glucose tolerance groups (normal glucose tolerance, impaired glucose tolerance or CF-related diabetes) and stratified in 3 groups according to the variation of their glucose tolerance: stable, improved or deteriorated. At baseline, patients in the deteriorated group had a better sensitivity to insulin than those in the improved group (P=0.029). At follow-up glucose tolerance remained stable in 55.3%, improved in 14.5% and deteriorated in 30.3% of patients. During follow-up, insulin secretion remained stable in all 3 groups. While insulin sensitivity remained stable in patients without changes in glucose tolerance it worsened in patients who deteriorated glucose tolerance (P<0.001) and improved in patients who improved their glucose tolerance (P=0.003). In a context of significantly reduced insulin secretion, variations of insulin sensitivity are associated with variations of glucose tolerance in adult patients with CF. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Enhanced lipid production in thermo-tolerant mutants of Chlorella pyrenoidosa NCIM 2738.

PubMed

Sachdeva, Neha; Gupta, Ravi Prakash; Mathur, Anshu Shankar; Tuli, Deepak Kumar

2016-12-01

The present study aimed to develop thermo-tolerant mutants of Chlorella pyrenoidosa NCIM 2738 for high lipids production. For this, ethyl methane sulfonate was used, which generated two effective thermo-tolerant mutants, M18 and M24 of Chlorella pyrenoidosa NCIM 2738, capable of surviving at temperature up to 47°C and showing improved lipid and biomass yields. They showed 59.62% and 50.75% increase, respectively in lipid content compared to wild type at 30°C, which could not grow at temperature above 35°C. The novelty of this study lied in incorporation of PAM Flurometry with mutagenesis to generate thermo-tolerant mutants of C. pyrenoidosa and investigating the reasons for increased yields of mutants at cellular and photosynthetic levels with the aim to use them for commercial biodiesel production. Copyright © 2016 Elsevier Ltd. All rights reserved.

[A study on training method for increasing adaptability to blood redistribution in human].

PubMed

Wu, Bin; You, Guang-xing; Wu, Ping; Xue, Yue-ying; Liu, Xing-hua; Su, Shuang-ning

2003-01-01

To verify validity of the increase in adaptability of blood redistribution in human body with repeated body position change training and to find preferable training method for increasing astronaut's adaptability of blood redistribution. Twelve subjects were randomly divided into group A and B. Six subjects in each group were trained with mode A and B repeated position change (9 times in 11 d) respectively. Their head-down tilt (HDT -30 degrees/30 min) tolerance and orthostatic tolerance were determined before and after training to verify training effects. 1) Two kinds of repeated body position change training modes increased all subjects' HDT tolerance. Compared with pre-training, during HDT test subjects' symptom scores in group B were significantly lower than those in group A (P<0.05) and after training decreasing magnitude of heart rate in group B increased significantly (P<0.01). Then mode B to be preferable training method in increasing HDT tolerance was suggested. 2) Two kinds of training modes improved all subjects' orthostatic tolerance. Compared with pre-training, during orthostatic tolerance test increasing magnitude of mean arterial blood pressure in group B increased significantly (P<0.05) and a trend of increasing magnitude of heart rate in group B was appeared smaller than in group A (P<0.10). Mode B to be preferable training method in increasing orthostatic tolerance was suggested too. Repeated body position change training could increase adaptability to blood redistribution in human body. Mode B was preferable training method and would be hopeful to be used in astronaut training.

Halopriming of seeds imparts tolerance to NaCl and PEG induced stress in Vigna radiata (L.) Wilczek varieties.

PubMed

Jisha, K C; Puthur, Jos T

2014-07-01

The investigation was carried out to study the effect of halopriming on NaCl and polyethylene glycol-6000 (PEG-6000) induced stress tolerance potential of three Vigna radiata (L.) Wilczek varieties, with varied abiotic stress tolerance potential. Halopriming is a seed priming technique in which the seeds were soaked in various salt solutions (in this study NaCl was used). The results of the study indicated that the application of stresses (both NaCl and PEG) induced retardation of growth attributes (measured in terms of shoot length, fresh weight, dry weight) and decrease in physiological attributes like total chlorophyll content, metabolites, photosynthetic and mitochondrial activity of the seedlings in all three V. radiata (L.) varieties. However, halopriming of the seeds could reduce the extent of decrease in these biological attributes. NaCl and PEG stress also caused increase in MDA content (a product of membrane lipid peroxidation) in all the varieties studied and this increase was significantly minimized under halopriming. From the present investigation it was evident that among the green gram varieties studied, Pusa Vishal, a NaCl tolerant variety showed enhanced tolerance to NaCl and PEG induced stress, when the seeds were subjected to halopriming followed by Pusa Ratna (stress sensitive variety). Pusa 9531 (drought tolerant variety) also showed positive halopriming effects but it was less significant when compared to other two varieties. It could be concluded that halopriming improved the drought and salinity stress tolerance potential of all varieties and it was significantly higher in the Pusa Vishal as compared to Pusa 9531 and Pusa Ratna.

Treatment tolerance and patient-reported outcomes favor online hemodiafiltration compared to high-flux hemodialysis in the elderly.

PubMed

Morena, Marion; Jaussent, Audrey; Chalabi, Lotfi; Leray-Moragues, Hélène; Chenine, Leila; Debure, Alain; Thibaudin, Damien; Azzouz, Lynda; Patrier, Laure; Maurice, Francois; Nicoud, Philippe; Durand, Claude; Seigneuric, Bruno; Dupuy, Anne-Marie; Picot, Marie-Christine; Cristol, Jean-Paul; Canaud, Bernard

2017-06-01

Large cohort studies suggest that high convective volumes associated with online hemodiafiltration may reduce the risk of mortality/morbidity compared to optimal high-flux hemodialysis. By contrast, intradialytic tolerance is not well studied. The aim of the FRENCHIE (French Convective versus Hemodialysis in Elderly) study was to compare high-flux hemodialysis and online hemodiafiltration in terms of intradialytic tolerance. In this prospective, open-label randomized controlled trial, 381 elderly chronic hemodialysis patients (over age 65) were randomly assigned in a one-to-one ratio to either high-flux hemodialysis or online hemodiafiltration. The primary outcome was intradialytic tolerance (day 30-day 120). Secondary outcomes included health-related quality of life, cardiovascular risk biomarkers, morbidity, and mortality. During the observational period for intradialytic tolerance, 85% and 84% of patients in high-flux hemodialysis and online hemodiafiltration arms, respectively, experienced at least one adverse event without significant difference between groups. As exploratory analysis, intradialytic tolerance was also studied, considering the sessions as a statistical unit according to treatment actually received. Over a total of 11,981 sessions, 2,935 were complicated by the occurrence of at least one adverse event, with a significantly lower occurrence in online hemodiafiltration with fewer episodes of intradialytic symptomatic hypotension and muscle cramps. By contrast, health-related quality of life, morbidity, and mortality were not different in both groups. An improvement in the control of metabolic bone disease biomarkers and β2-microglobulin level without change in serum albumin concentration was observed with online hemodiafiltration. Thus, overall outcomes favor online hemodiafiltration over high-flux hemodialysis in the elderly. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

The Effects of Dietary Iron and Capsaicin on Hemoglobin, Blood Glucose, Insulin Tolerance, Cholesterol, and Triglycerides, in Healthy and Diabetic Wistar Rats.

PubMed

Márquez-Ibarra, Adriana; Huerta, Miguel; Villalpando-Hernández, Salvador; Ríos-Silva, Mónica; Díaz-Reval, María I; Cruzblanca, Humberto; Mancilla, Evelyn; Trujillo, Xóchitl

2016-01-01

Our aim was to assess the effects of dietary iron, and the compound capsaicin, on hemoglobin as well as metabolic indicators including blood glucose, cholesterol, triglycerides, insulin, and glucose tolerance. Our animal model was the Wistar rat, fed a chow diet, with or without experimentally induced diabetes. Diabetic males were fed control, low, or high-iron diets, the latter, with or without capsaicin. Healthy rats were fed identical diets, but without the capsaicin supplement. We then measured the parameters listed above, using the Student t-test and ANOVA, to compare groups. Healthy rats fed a low-iron diet exhibited significantly reduced total cholesterol and triglyceride levels, compared with rats fed a control diet. Significantly reduced blood lipid was also provoked by low dietary iron in diabetic rats, compared with those fed a control diet. Insulin, and glucose tolerance was only improved in healthy rats fed the low-iron diet. Significant increases in total cholesterol were found in diabetic rats fed a high-iron diet, compared with healthy rats fed the same diet, although no statistical differences were found for triglycerides. Hemoglobin levels, which were not statistically different in diabetic versus healthy rats fed the high-iron diet, fell when capsaicin was added. Capsaicin also provoked a fall in the level of cholesterol and triglycerides in diabetic animals, versus diabetics fed with the high iron diet alone. In conclusion, low levels of dietary iron reduced levels of serum triglycerides, hemoglobin, and cholesterol, and significantly improved insulin, and glucose tolerance in healthy rats. In contrast, a high-iron diet increased cholesterol significantly, with no significant changes to triglyceride concentrations. The addition of capsaicin to the high-iron diet (for diabetic rats) further reduced levels of hemoglobin, cholesterol, and triglycerides. These results suggest that capsaicin, may be suitable for the treatment of elevated hemoglobin, in patients.

Are gastroenterologists less tolerant of treatment risks than patients? Benefit-risk preferences in Crohn's disease management.

PubMed

Johnson, F Reed; Hauber, Brett; Özdemir, Semra; Siegel, Corey A; Hass, Steven; Sands, Bruce E

2010-10-01

Crohn's disease is a serious and debilitating gastrointestinal disorder with a high, unmet need for new treatments. Biologic agents have the potential to alter the natural course of Crohn's disease but present known risks of potential serious adverse events (SAEs). Previous studies have shown that patients are willing to accept elevated SAE risks in exchange for clinical efficacy. Gastroenterologists and patients may have similar goals of maximizing treatment benefit while minimizing risk; however, gastroenterologists may assess the relative importance of risk differently than patients. To (a) understand how gastroenterologists caring for patients with Crohn's disease balance benefits and risks in their treatment decisions and (b) compare their treatment preferences with those of adult patients with Crohn's disease. Both patient and gastroenterologist treatment preferences were elicited using a web-based, choice-format conjoint survey instrument. The conjoint questions required subjects to choose between 2 hypothetical treatment options with differing levels of treatment attributes. Patients evaluated the treatment options for themselves, and gastroenterologists evaluated the treatment options for each of 3 hypothetical patient types: (a) female aged 25 years with no history of Crohn's disease surgery (young), (b) male aged 45 years with 1 Crohn's disease surgery (middleaged), and (c) female older than 70 years with 4 Crohn's disease surgeries (older). Treatment attributes represented the expected outcomes of treatment: severity of daily symptoms, frequency of flare-ups, serious disease complications, oral steroid use, and the risks of 3 potentially fatal SAEs - lymphoma, serious or opportunistic infections, and progressive multifocal leukoencephalopathy (PML) - during 10 years of treatment. Maximum acceptable risk (MAR), defined as the highest level of SAE risk that subjects would accept in return for a given improvement in efficacy (i.e., the increase in treatment risk that exactly offsets the hypothetical increase in treatment benefit), was calculated using preference weights (parameter marginal log odds ratios) that were estimated with conjoint analysis (random parameters logit models). Gastroenterologists' and patients' mean MARs for 3 SAE risks were calculated for 6 improvements in Crohn's disease symptoms, and gastroenterologists' preference weights for each of the 3 patient profiles were compared. Gastroenterologists' MARs for a hypothetical middle-aged patient were then compared with predicted MARs derived using data from the patient study for male patients aged 40 to 50 years with 1 surgery. After exclusion of nonrespondents (n = 4,021 of 4,422 gastroenterologists; n = 681 of 1,285 patients) and nonevaluable respondents (n = 86 gastroenterologists; n = 24 patients), 315 gastroenterologists and 580 patients were included in the final analytic samples. There were no statistically significant differences in gastroenterologists' preference weights for the middle-aged versus young patient profiles. However, preference weights indicated that gastroenterologists are more concerned about 5% side-effect risks for the older patient profile than for the middle-aged patient profile. For symptomatic improvements from severe symptoms to remission, gastroenterologists' highest MARs were for lymphoma: 6.21%, 8.99%, and 25.00% for the young, middle-aged, and older patient types, respectively. In analyses of improvements from severe to moderate symptoms and from moderate symptoms to remission for hypothetical middle-aged patients, gastroenterologists' 10-year risk tolerance ranged between 1.96% lymphoma risk in return for an improvement from moderate symptoms to remission and 4.93% lymphoma risk for an improvement from severe to moderate symptoms; patients' 10-year risk tolerance for middle-aged patients ranged between 1.52% PML risk in return for an improvement from severe to moderate symptoms and 5.86% infection risk for an improvement from moderate symptoms to remission. On average, gastroenterologists and patients disagreed about how much risk is tolerable for improvements in efficacy. In exchange for improvements from severe to moderate symptoms for the middle-aged patient profile, gastroenterologists were significantly more tolerant than patients of treatment risks of PML (P < 0.001) and serious infection (P = 0.001) but not lymphoma (P = 0.230). In contrast, in exchange for improvements from moderate symptoms to remission for the same patient profile, patients were significantly more tolerant than gastroenterologists of treatment risks for serious infection (P < 0.001) and lymphoma (P < 0.001) but not PML (P = 0.158). Gastroenterologists and patients have well-defined preferences among treatment attributes and are willing to accept tradeoffs between efficacy and treatment risks. However, risk tolerance varies depending on the type of patient for whom gastroenterologists are being asked to consider treatment. In rating treatment preferences for patients with a middle-aged profile, gastroenterologists are less tolerant of SAE risks than patients in exchange for improvement from moderate symptoms to remission.

Exogenous Melatonin Mitigates Acid Rain Stress to Tomato Plants through Modulation of Leaf Ultrastructure, Photosynthesis and Antioxidant Potential.

PubMed

Debnath, Biswojit; Hussain, Mubasher; Irshad, Muhammad; Mitra, Sangeeta; Li, Min; Liu, Shuang; Qiu, Dongliang

2018-02-11

Acid rain (AR) is a serious global environmental issue causing physio-morphological changes in plants. Melatonin, as an indoleamine molecule, has been known to mediate many physiological processes in plants under different kinds of environmental stress. However, the role of melatonin in acid rain stress tolerance remains inexpressible. This study investigated the possible role of melatonin on different physiological responses involving reactive oxygen species (ROS) metabolism in tomato plants under simulated acid rain (SAR) stress. SAR stress caused the inhibition of growth, damaged the grana lamella of the chloroplast, photosynthesis, and increased accumulation of ROS and lipid peroxidation in tomato plants. To cope the detrimental effect of SAR stress, plants under SAR condition had increased both enzymatic and nonenzymatic antioxidant substances compared with control plants. But such an increase in the antioxidant activities were incapable of inhibiting the destructive effect of SAR stress. Meanwhile, melatonin treatment increased SAR-stress tolerance by repairing the grana lamella of the chloroplast, improving photosynthesis and antioxidant activities compared with those in SAR-stressed plants. However, these possible effects of melatonin are dependent on concentration. Moreover, our study suggests that 100-μM melatonin treatment improved the SAR-stress tolerance by increasing photosynthesis and ROS scavenging antioxidant activities in tomato plants.

Effect of Ezetimibe on Insulin Secretion in db/db Diabetic Mice

PubMed Central

Zhong, Yong; Wang, Jun; Gu, Ping; Shao, Jiaqing; Lu, Bin; Jiang, Shisen

2012-01-01

Objective. To investigate the effect of ezetimibe on the insulin secretion in db/db mice. Methods. The db/db diabetic mice aged 8 weeks were randomly assigned into 2 groups and intragastrically treated with ezetimibe or placebo for 6 weeks. The age matched db/m mice served as controls. At the end of experiment, glucose tolerance test was performed and then the pancreas was collected for immunohistochemistry. In addition, in vitro perfusion of pancreatic islets was employed for the detection of insulin secretion in the first phase. Results. In the ezetimibe group, the fasting blood glucose was markedly reduced, and the total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were significantly lowered when compared with those in the control group (P < 0.05). At 120 min after glucose tolerance test, the area under curve in the ezetimibe group was significantly smaller than that in the control group (P < 0.05), but the AUCINS0−30 was markedly higher. In vitro perfusion of pancreatic islets revealed the first phase insulin secretion was improved. In addition, the insulin expression in the pancreas in the ezetimibe group was significantly increased as compared to the control group. Conclusion. Ezetimibe can improve glucose tolerance, recover the first phase insulin secretion, and protect the function of β cells in mice. PMID:23118741

Use of arbuscular mycorrhizal fungi to improve the drought tolerance of Cupressus atlantica G.

PubMed

Zarik, Lamia; Meddich, Abdelilah; Hijri, Mohamed; Hafidi, Mohamed; Ouhammou, Ahmed; Ouahmane, Lahcen; Duponnois, Robin; Boumezzough, Ali

2016-01-01

In this study, we investigated whether indigenous arbuscular mycorrhizal (AM) fungi could improve the tolerance of Cupressus atlantica against water deficit. We tested a gradient of watering regime spanning from 90% to 25% of soil retention capacity of water on mycorhized and non-mycorhized seedlings in pot cultures with sterilized and non-sterilized soils. Our result showed a positive impact of AM fungi on shoot height, stem diameter and biomass as well as on the growth rate. We also observed that inoculation with AM fungi significantly improved uptake of minerals by C. atlantica in both sterilized and non-sterilized soils independently of water regimes. We found that mycorhized plants maintained higher relative water content (RWC) and water potential compared with non-mycorhized plants that were subjected to drought-stress regimes (50% and 25% of soil retention capacity). The contents of proline and of soluble sugars showed that their concentrations decreased in non-mycorhized plants subjected to DS. Superoxide dismutase (SOD) and catalase (CAT) activities also decreased in non-mycorhized plants submitted to DS compared to mycorhized plants. The same pattern was observed by measuring peroxidase (POD) enzyme activity. The results demonstrated that AM fungal inoculation promoted the growth and tolerance of C. atlantica against DS in pot cultures. Therefore, mycorrhizal inoculation could be a potential solution for the conservation and reestablishment of C. atlantica in its natural ecosystem. Copyright © 2016 Académie des sciences. Published by Elsevier SAS. All rights reserved.

Improved Tolerance to a New Amino Acid-Based Formula by Infants With Cow's Milk Protein Allergy.

PubMed

Jirapinyo, Pipop; Densupsoontorn, Narumon; Kangwanpornsiri, Channagan; Wongarn, Renu; Tirapongporn, Hathaichanok; Chotipanang, Kwanjai; Phuangphan, Phakkanan

2016-12-01

Prevalence and severity of cow's milk protein allergy (CMA) in infants are increasing. A proportion of infants with CMA still elicit signs and symptoms of CMA while ingesting commercial amino acid-based formulas (AAFs). We propose that protein in glucose polymers (GPs) derived from corn starch in the AAFs might be the cause of intolerance to AAF in some infants. We thus have produced small molecules of GPs from rice starch, eliminating the protein fraction from them, and subsequently used them as the sole source of carbohydrate in a new amino acid-based formula (NAAF). The efficacy of the NAAF was compared with that of an AAF in a double-blind, placebo-controlled food challenge (DBPCFC) in young infants with CMA aged <4 months. Infants consumed each formula for 14 days before switching to the other one. If no respiratory, dermatologic, and gastrointestinal symptom occurred, it was considered tolerance. After the challenge, infants consumed the tolerated formula for 4 weeks to prove real tolerance to that formula. Of 46 infants, 23 were intolerant to the AAF, of whom 7 (30.4%) were also intolerant to the NAAF. Sixteen of the 23 infants who were intolerant to the AAF could tolerate the NAAF ( P < .05). The minimal important difference of decreasing percentage of intolerance to the NAAF was 34.8% compared with the infants who were intolerant to the AAF. The NAAF is better tolerated than a commercially available AAF for the management of infants with CMA.

Pharmacology of the glucagon-like peptide-1 analog exenatide extended-release in healthy cats.

PubMed

Rudinsky, A J; Adin, C A; Borin-Crivellenti, S; Rajala-Schultz, P; Hall, M J; Gilor, C

2015-04-01

Exenatide extended-release (ER) is a microencapsulated formulation of the glucagon-like peptide 1-receptor agonist exenatide. It has a protracted pharmacokinetic profile that allows a once-weekly injection with comparable efficacy to insulin with an improved safety profile in type II diabetic people. Here, we studied the pharmacology of exenatide ER in 6 healthy cats. A single subcutaneous injection of exenatide ER (0.13 mg/kg) was administered on day 0. Exenatide concentrations were measured for 12 wk. A hyperglycemic clamp (target = 225 mg/dL) was performed on days -7 (clamp I) and 21 (clamp II) with measurements of insulin and glucagon concentrations. Glucose tolerance was defined as the amount of glucose required to maintain hyperglycemia during the clamp. Continuous glucose monitoring was performed on weeks 0, 2, and 6 after injection. Plasma concentrations of exenatide peaked at 1 h and 4 wk after injection. Comparing clamp I with clamp II, fasting blood glucose decreased (mean ± standard deviation = -11 ± 8 mg/dL, P = 0.02), glucose tolerance improved (median [range] +33% [4%-138%], P = 0.04), insulin concentrations increased (+36.5% [-9.9% to 274.1%], P = 0.02), and glucagon concentrations decreased (-4.7% [0%-12.1%], P = 0.005). Compared with preinjection values on continuous glucose monitoring, glucose concentrations decreased and the frequency of readings <50 mg/dL increased at 2 and 6 wk after injection of exenatide ER. This did not correspond to clinical hypoglycemia. No other side effects were observed throughout the study. Exenatide ER was safe and effective in improving glucose tolerance 3 wk after a single injection. Further evaluation is needed to determine its safety, efficacy, and duration of action in diabetic cats. Copyright © 2015 Elsevier Inc. All rights reserved.

Metabolic and hormonal changes induced by pioglitazone in polycystic ovary syndrome: a randomized, placebo-controlled clinical trial.

PubMed

Aroda, Vanita R; Ciaraldi, Theodore P; Burke, Paivi; Mudaliar, Sunder; Clopton, Paul; Phillips, Susan; Chang, R Jeffrey; Henry, Robert R

2009-02-01

Polycystic ovary syndrome (PCOS) is characterized by insulin resistance, compensatory hyperinsulinemia, increased prevalence of impaired glucose tolerance, and increased ovarian androgen biosynthesis. The aim of the study was to evaluate effects of pioglitazone on whole body insulin action and ovarian androgen biosynthesis in PCOS. We performed a randomized placebo-controlled trial. The study was conducted at the Special Diagnostic and Treatment Unit of the Veterans Affairs Medical Center, San Diego, and the University of California, San Diego, General Clinical Research Center. A total of 23 subjects with PCOS were evaluated at baseline and end of treatment. Six age- and body mass index-matched women without PCOS were normal controls for baseline evaluation. Subjects with PCOS were randomized to oral placebo or pioglitazone 45 mg daily for 6 months. The primary outcome measures were whole body insulin action as measured by hyperinsulinemic euglycemic clamp and ovarian androgen biosynthesis as measured by leuprolide-stimulated production of 17-hydroxyprogesterone (17-OHP). Compared with placebo, pioglitazone treatment significantly improved multiple measures of insulin action, including glucose disposal rate (P < 0.01), 2-h glucose during 75-g oral glucose tolerance test (P < 0.01), area under the curve glucose during oral glucose tolerance test (P < 0.01), serum adiponectin (P < 0.01), and fasting hyperinsulinemia (P < 0.01). Compared to placebo, pioglitazone treatment reduced the increment of leuprolide-stimulated 17-OHP (P < 0.02). Improvements in glucose disposal rate correlated with reductions in 17-OHP stimulation (P < 0.02). Compared to placebo, pioglitazone treatment in PCOS was associated with improvements in insulin action and glucose homeostasis and ameliorated the hyperandrogenic ovarian response.

Randomized, clinical trial of RT001: Early signals of efficacy in Friedreich's ataxia.

PubMed

Zesiewicz, Theresa; Heerinckx, Frederic; De Jager, Robert; Omidvar, Omid; Kilpatrick, Marcus; Shaw, Jessica; Shchepinov, Mikhail S

2018-04-06

RT001 is a deuterated ethyl linoleate that inhibits lipid peroxidation and is hypothesized to reduce cellular damage and recover mitochondrial function in degenerative diseases such as Friedreich's ataxia. To evaluate the safety, pharmacokinetics, and preliminary efficacy of RT001 in Friedreich's ataxia patients. We conducted a phase I/II double-blind, comparator-controlled trial with 2 doses of RT001 in Friedreich's ataxia patients (9 subjects each cohort). Subjects were randomized 2:1 to receive either RT001 (1.8 or 9.0 g/day), or a matching dose of nondeuterated ethyl linoleate as comparator for 28 days. The primary endpoints were safety, tolerability, and pharmacokinetic analysis. Secondary endpoints included cardiopulmonary exercise testing and timed 25-foot walk. Nineteen patients enrolled in the trial, and 18 completed all safety and efficacy measurements. RT001 was found to be safe and tolerable, with plasma levels approaching saturation by 28 days. One subject with a low body mass index experienced steatorrhea taking a high dose and discontinued the study. Deuterated arachidonic acid (a brain-penetrant metabolite of RT001) was found to be present in plasma on day 28. There was an improvement in peak workload in the drug group compared to placebo (0.16 watts/kg; P = 0.008), as well as an improvement trend in peak oxygen consumption (change of 0.16 L/min; P = 0.116), and in stride speed (P = 0.15). RT001 was found to be safe and tolerable over 28 days, and improved peak workload. Further research into the effect of RT001 in Friedreich's ataxia is warranted. © 2018 International Parkinson and Movement Disorder Society. © 2018 International Parkinson and Movement Disorder Society.

GABA dramatically improves glucose tolerance in streptozotocin-induced diabetic rats fed with high-fat diet.

PubMed

Sohrabipour, Shahla; Sharifi, Mohammad Reza; Talebi, Ardeshir; Sharifi, Mohammadreza; Soltani, Nepton

2018-05-05

Skeletal muscle, hepatic insulin resistance, and beta cell dysfunction are the characteristic pathophysiological features of type 2 diabetes mellitus. GABA has an important role in pancreatic islet cells. The present study attempted to clarify the possible mechanism of GABA to improve glucose tolerance in a model of type 2 diabetes mellitus in rats. Fifty Wistar rats were divided into five groups: NDC that was fed the normal diet, CD which received a high-fat diet with streptozotocin, CD-GABA animals that received GABA via intraperitoneal injection, plus CD-Ins1 and CD-Ins2 groups which were treated with low and high doses of insulin, respectively. Body weight and blood glucose were measured weekly. Intraperitoneal glucose tolerance test (IPGTT), insulin tolerance test (ITT), urine volume, amount of water drinking, and food intake assessments were performed monthly. The hyperinsulinemic euglycemic clamp was done for assessing insulin resistance. Plasma insulin and glucagon were measured. Abdominal fat was measured. Glucagon receptor, Glucose 6 phosphatase, Phosphoenolpyruvate carboxykinase genes expression were evaluated in liver and Glucose transporter 4 (GLUT4) genes expression and protein translocation were evaluated in the muscle. GABA or insulin therapy improved blood glucose, insulin level, IPGTT, ITT, gluconeogenesis pathway, Glucagon receptor, body weight and body fat in diabetic rats. GLUT4 gene and protein expression increased. GABA whose beneficial effect was comparable to that of insulin, also increased glucose infusion rate during an euglycemic clamp. GABA could improve insulin resistance via rising GLUT4 and also decreasing the gluconeogenesis pathway and Glucagon receptor gene expression. Copyright © 2018. Published by Elsevier B.V.

Arabidopsis Enhanced Drought Tolerance1/HOMEODOMAIN GLABROUS11 Confers Drought Tolerance in Transgenic Rice without Yield Penalty1[W][OA

PubMed Central

Yu, Linhui; Chen, Xi; Wang, Zhen; Wang, Shimei; Wang, Yuping; Zhu, Qisheng; Li, Shigui; Xiang, Chengbin

2013-01-01

Enhancing drought tolerance without yield decrease has been a great challenge in crop improvement. Here, we report the Arabidopsis (Arabidopsis thaliana) homodomain-leucine zipper transcription factor Enhanced Drought Tolerance/HOMEODOMAIN GLABROUS11 (EDT1/HDG11) was able to confer drought tolerance and increase grain yield in transgenic rice (Oryza sativa) plants. The improved drought tolerance was associated with a more extensive root system, reduced stomatal density, and higher water use efficiency. The transgenic rice plants also had higher levels of abscisic acid, proline, soluble sugar, and reactive oxygen species-scavenging enzyme activities during stress treatments. The increased grain yield of the transgenic rice was contributed by improved seed setting, larger panicle, and more tillers as well as increased photosynthetic capacity. Digital gene expression analysis indicated that AtEDT1/HDG11 had a significant influence on gene expression profile in rice, which was consistent with the observed phenotypes of transgenic rice plants. Our study shows that AtEDT1/HDG11 can improve both stress tolerance and grain yield in rice, demonstrating the efficacy of AtEDT1/HDG11 in crop improvement. PMID:23735506

Tolerability of clindamycin/tretinoin gel vs. tretinoin microsphere gel and adapalene gel.

PubMed

Leyden, James; Wortzman, Mitchell; Baldwin, Edward K

2009-04-01

Newer agents and formulations seek to improve the tolerability of topical retinoid therapy. Recently, a gel containing crystalline clindamycin 1.2% and tretinoin 0.025% (CLIN/RA) was approved by the U.S. Food and Drug Administration (FDA) for the treatment of treating mild-to-moderate acne. This single-center, randomized, evaluator-blind phase 1 study compared the tolerability of CLIN/RA to 0.1% tretinoin gel or 0.1% adapalene gel. Forty-five patients applied CLIN/RA once daily to one side of their face every day for 21 days. Patients were randomized to either tretinoin 0.1% (n = 23) or adapalene 0.1% (n = 22) on the contralateral side. A clinical evaluator assessed degree of erythema and scaling; patients provided subjective evaluations of burning, stinging, and itching. CLIN/RA was significantly better tolerated than was 0.1% tretinoin gel, as evidenced by significantly reduced erythema (P < 0.04), scaling (P < 0.03), itching (P < 0.02), burning (P < 0.03) and stinging (P < 0.04). A trend for greater erythema, scaling, and subjective discomfort for 0.1% adapalene gel compared to CLIN/RA was also evident.

Different cultivation methods to acclimatise ammonia-tolerant methanogenic consortia.

PubMed

Tian, Hailin; Fotidis, Ioannis A; Mancini, Enrico; Angelidaki, Irini

2017-05-01

Bioaugmentation with ammonia tolerant-methanogenic consortia was proposed as a solution to overcome ammonia inhibition during anaerobic digestion process recently. However, appropriate technology to generate ammonia tolerant methanogenic consortia is still lacking. In this study, three basic reactors (i.e. batch, fed-batch and continuous stirred-tank reactors (CSTR)) operated at mesophilic (37°C) and thermophilic (55°C) conditions were assessed, based on methane production efficiency, incubation time, TAN/FAN (total ammonium nitrogen/free ammonia nitrogen) levels and maximum methanogenic activity. Overall, fed-batch cultivation was clearly the most efficient method compared to batch and CSTR. Specifically, by saving incubation time up to 150%, fed-batch reactors were acclimatised to nearly 2-fold higher FAN levels with a 37%-153% methanogenic activity improvement, compared to batch method. Meanwhile, CSTR reactors were inhibited at lower ammonia levels. Finally, specific methanogenic activity test showed that hydrogenotrophic methanogens were more active than aceticlastic methanogens in all FAN levels above 540mgNH 3 -NL -1 . Copyright © 2017 Elsevier Ltd. All rights reserved.

Topical treatment of tinea pedis using 6% coriander oil in unguentum leniens: a randomized, controlled, comparative pilot study.

PubMed

Beikert, F C; Anastasiadou, Z; Fritzen, B; Frank, U; Augustin, M

2013-01-01

The antifungal activity of coriander oil has already been demonstrated in vitro. Evaluation of the efficacy and tolerability of 6% coriander oil in unguentum leniens in the treatment of interdigital tinea pedis. Half-side comparative pilot study on subjects with symmetric, bilateral interdigital tinea pedis. Active drug and placebo control were applied twice daily on the affected areas, and follow-up visits were performed on days 14 and 28. 40 participants (mean age 52.5 years, 60% male) were included in the study. For 6% coriander oil in unguentum leniens, a highly significant improvement of the clinical signs (p < 0.0001) was observed during the entire observation period; the number of positive fungal cultures also tended to decrease (p = 0.0654). The tolerability of the tested substances was good. Coriander oil is effective and well tolerated in the treatment of interdigital tinea pedis. Copyright © 2013 S. Karger AG, Basel.

Integrated Physiological Mechanisms of Exercise Performance, Adaptation, and Maladaptation to Heat Stress

DTIC Science & Technology

2011-10-01

performance. We discuss novel systemic (heat acclimation) and cellular ( acquired thermal tolerance) adaptations that improve performance in hot and...cellular ( acquired thermal tolerance) adaptations that improve perfor- mance in hot and temperate environments and protect organs from heat stroke as...performance; (iii) newly identified adaptations associated with heat accli- mation/ acquired thermal tolerance that impact exercise-heat tolerance; (iv

Effects of Starvation and Thermal Stress on the Thermal Tolerance of Silkworm, Bombyx mori: Existence of Trade-offs and Cross-Tolerances.

PubMed

Mir, A H; Qamar, A

2017-09-27

Organisms, in nature, are often subjected to multiple stressors, both biotic and abiotic. Temperature and starvation are among the main stressors experienced by organisms in their developmental cycle and the responses to these stressors may share signaling pathways, which affects the way these responses are manifested. Temperature is a major factor governing the performance of ectothermic organisms in ecosystems worldwide and, therefore, the thermal tolerance is a central issue in the thermobiology of these organisms. Here, we investigated the effects of starvation as well as mild heat and cold shocks on the thermal tolerance of the larvae of silkworm, Bombyx mori (Linnaeus). Starvation acted as a meaningful or positive stressor as it improved cold tolerance, measured as chill coma recovery time (CCRT), but, at the same time, it acted as a negative stressor and impaired the heat tolerance, measured as heat knockdown time (HKT). In the case of heat tolerance, starvation negated the positive effects of both mild cold as well as mild heat shocks and thus indicated the existence of trade-off between these stressors. Both mild heat and cold shocks improved the thermal tolerance, but the effects were more prominent when the indices were measured in response to a stressor of same type, i.e., a mild cold shock improved the cold tolerance more than the heat tolerance and vice versa. This improvement in thermal tolerance by both mild heat as well as cold shocks indicated the possibility of cross-tolerance between these stressors.

Establishment and application of a modified membrane-blot assay for Rhizomucor miehei lipases aimed at improving their methanol tolerance and thermostability.

PubMed

He, Dong; Luo, Wen; Wang, Zhiyuan; Lv, Pengmei; Yuan, Zhenhong; Huang, Shaowei; Xv, Jingliang

2017-07-01

Directed evolution has been proved an effective way to improve the stability of proteins, but high throughput screening assays for directed evolution with simultaneous improvement of two or more properties are still rare. In this study, we aimed to establish a membrane-blot assay for use in the high-throughput screening of Rhizomucor miehei lipases (RMLs). With the assistance of the membrane-blot screening assay, a mutant E47K named G10 that showed improved thermal stability was detected in the first round of error-prone PCR. Using G10 as the parent, two variants G10-11 and G10-20 that showed improved thermal stability and methanol tolerance without loss of activity compared to the wild type RML were obtained. The T 50 60 -value of G10-11 and G10-20 increased by 12°C and 6.5°C, respectively. After incubation for 1h, the remaining residual activity of G10-11 and G10-20 was 63.45% and 74.33%, respectively, in 50% methanol, and 15.98% and 30.22%, respectively, in 80% methanol. Thus, we successfully developed a membrane-blot assay that could be used for the high-throughput screening of RMLs with improved thermostability and methanol tolerance. Based on our findings, we believe that our newly developed membrane-blot assay will have potential applications in directed evolution in the future. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of Mulching Tolerant Plant Straw on Soil Surface on Growth and Cadmium Accumulation of Galinsoga parviflora

PubMed Central

Lin, Lijin; Liao, Ming’an; Ren, Yajun; Luo, Li; Zhang, Xiao; Yang, Daiyu; He, Jing

2014-01-01

Pot and field experiments were conducted to study the effects of mulching with straw of cadmium (Cd) tolerant plants (Ranunculus sieboldii, Mazus japonicus, Clinopodium confine and Plantago asiatica) on growth and Cd accumulation of Galinsoga parviflora in Cd-contaminated soil. In the pot experiment, mulching with M. japonicus straw increased the root biomass, stem biomass, leaf biomass, shoot biomass, plant height and activities of antioxidant enzymes (superoxide dismutase, peroxidase and catalase) of G. parviflora compared with the control, whereas mulching with straws of R. sieboldii, C. confine and P. asiatica decreased these parameters. Straws of the four Cd-tolerant plants increased the Cd content in roots of G. parviflora compared with the control. However, only straws of M. japonicus and P. asiatica increased the Cd content in shoots of G. parviflora, reduced the soil pH, and increased the soil exchangeable Cd concentration. Straw of M. japonicus increased the amount of Cd extraction in stems, leaves and shoots of G. parviflora by 21.11%, 29.43% and 24.22%, respectively, compared with the control, whereas straws of the other three Cd-tolerant plants decreased these parameters. In the field experiment, the M. japonicus straw also increased shoot biomass, Cd content in shoots, and amount of Cd extraction in shoots of G. parviflora compared with the control. Therefore, straw of M. japonicus can be used to improve the Cd extraction ability of G. parviflora from Cd-contaminated soil. PMID:25490210

IrrE, a Global Regulator of Extreme Radiation Resistance in Deinococcus radiodurans, Enhances Salt Tolerance in Escherichia coli and Brassica napus

PubMed Central

Zhou, Zhengfu; Yan, Yongliang; Zhang, Wei; Lu, Wei; Ping, Shuzhen; Dai, Qilin; Yuan, Menglong; Feng, Bin; Hou, Xiaoguang; Zhang, Ying; Ruiqiang; Liu, Tingting; Feng, Lu; Wang, Lei; Chen, Ming; Lin, Min

2009-01-01

Background Globally, about 20% of cultivated land is now affected by salinity. Salt tolerance is a trait of importance to all crops in saline soils. Previous efforts to improve salt tolerance in crop plants have met with only limited success. Bacteria of the genus Deinococcus are known for their ability to survive highly stressful conditions, and therefore possess a unique pool of genes conferring extreme resistance. In Deinococcus radiodurans, the irrE gene encodes a global regulator responsible for extreme radioresistance. Methodology/Principal Findings Using plate assays, we showed that IrrE protected E. coli cells against salt shock and other abiotic stresses such as oxidative, osmotic and thermal shocks. Comparative proteomic analysis revealed that IrrE functions as a switch to regulate different sets of proteins such as stress responsive proteins, protein kinases, glycerol-degrading enzymes, detoxification proteins, and growth-related proteins in E. coli. We also used quantitative RT-PCR to investigate expression of nine selected stress-responsive genes in transgenic and wild-type Brassica napus plants. Transgenic B. napus plants expressing the IrrE protein can tolerate 350 mM NaCl, a concentration that inhibits the growth of almost all crop plants. Conclusions Expression of IrrE, a global regulator for extreme radiation resistance in D. radiodurans, confers significantly enhanced salt tolerance in both E. coli and B. napus. We thus propose that the irrE gene might be used as a potentially promising transgene to improve abiotic stress tolerances in crop plants. PMID:19204796

The Fungus Aspergillus aculeatus Enhances Salt-Stress Tolerance, Metabolite Accumulation, and Improves Forage Quality in Perennial Ryegrass

PubMed Central

Li, Xiaoning; Han, Shijuan; Wang, Guangyang; Liu, Xiaoying; Amombo, Erick; Xie, Yan; Fu, Jinmin

2017-01-01

Perennial ryegrass (Lolium perenne) is an important forage grass with high yield and superior quality in temperate regions which is widely used in parks, sport field, and other places. However, perennial ryegrass is moderately tolerant to salinity stress compared to other commercial cultivars and salt stress reduces their growth and productivity. Aspergillus aculeatus has been documented to participate in alleviating damage induced by salinity. Therefore, the objective of this study was to investigate the mechanisms underlying A. aculeatus-mediated salt tolerance, and forage quality of perennial ryegrass exposed to 0, 200, and 400 mM NaCl concentrations. Physiological markers and forage quality of perennial ryegrass to salt stress were evaluated based on the growth rate, photosynthesis, antioxidant enzymes activity, lipid peroxidation, ionic homeostasis, the nutritional value of forage, and metabolites. Plants inoculated with A. aculeatus exhibited higher relative growth rate (RGR), turf and forage quality under salt stress than un-inoculated plants. Moreover, in inoculated plants, the fungus remarkably improved plant photosynthetic efficiency, reduced the antioxidant enzymes activity (POD and CAT), and attenuated lipid peroxidation (decreased H2O2 and MDA accumulation) induced by salinity, compared to un-inoculated plants. Furthermore, the fungus also acts as an important role in maintaining the lower Na/K ratio and metabolites and lower the amino acids (Alanine, Proline, GABA, and Asparagine), and soluble sugars (Glucose and Fructose) for inoculated plants than un-inoculated ones. Our results suggest that A. aculeatus may be involved in modulating perennial ryegrass tolerance to salinity in various ways. PMID:28936200

Tetraploid Carrizo citrange rootstock (Citrus sinensis Osb.×Poncirus trifoliata L. Raf.) enhances natural chilling stress tolerance of common clementine (Citrus clementina Hort. ex Tan).

PubMed

Oustric, Julie; Morillon, Raphaël; Luro, François; Herbette, Stéphane; Lourkisti, Radia; Giannettini, Jean; Berti, Liliane; Santini, Jérémie

2017-07-01

Low temperatures can disturb the development, growth and geographic distribution of plants, particularly cold-sensitive plants in the Mediterranean area, where temperatures can reach seasonally low levels. In citrus crops, scion/rootstock combinations are used to improve fruit production and quality, and increase tolerance to biotic and abiotic stresses. In the last decade, several studies have shown that tetraploid citrus seedlings or rootstocks are more tolerant to abiotic stress than their respective diploid. The objective of this study was to test whether the use of tetraploid rootstocks can improve the chilling tolerance of the scion. We compared physiological and biochemical responses to low seasonal temperatures of common Clementine (Citrus sinensis Osb.×Poncirus trifoliata L. Raf.) grafted on diploid and tetraploid Carrizo citrange rootstocks, named C/2xCC and C/4xCC, respectively. During the coldest months, C/4xCC showed a smaller decrease in net photosynthesis (Pn), stomatal conductance (G s ), chlorophyll fluorescence (F v /F m ), and starch levels, and lower levels of malondialdehyde and electrolyte leakage than C/2xCC. Specific activities of catalase (CAT), ascorbate peroxidase (APX) and dehydroascorbate reductase (DHAR) were higher in C/4xCC during the cold period, whereas chlorophyll, proline, ascorbate and hydrogen peroxide (H 2 O 2 ) levels and superoxide dismutase (SOD) activity did not vary significantly between C/4xCC and C/2xCC throughout the study period. Taken together, these results demonstrate that tetraploid Carrizo citrange rootstock improves the chilling tolerance of common clementine (scion) thanks to a part of the antioxidant system. Copyright © 2017. Published by Elsevier GmbH.

2 L PEG plus ascorbic acid versus 4 L PEG plus simethicon for colonoscopy preparation: a randomized single-blind clinical trial.

PubMed

Gentile, Maurizio; De Rosa, Michele; Cestaro, Giovanni; Forestieri, Pietro

2013-06-01

The 2 L polyethylene glycol (PEG) lavage solution has been proved to be similarly safe and effective as 4 L PEG formulations, in spite of the reduced volume. To compare low-volume PEG-based solution combined with ascorbic acid with high-volume PEG-based solution combined with simethicon in terms of efficacy and patient tolerability. This was a single-blind prospective randomized trial. Patients were randomized to receive either 2 L PEG plus ascorbic acid (PEG+Asc) or 4 L PEG plus simethicon (PEG+Sim). The primary endpoint was overall colon cleansing evaluation, assessed by blinded investigators using Aronchick score. Secondary end points included patient compliance and tolerability and adverse events. Sixty patients received PEG+Asc and 60 received PEG+Sim. Overall bowel cleansing score was considered adequate in 81.67% of the PEG+Asc and 80% of the PEG+Sim groups, respectively. Excellent and good ratings were recorded in 11.6% and 38.3% receiving PEG+Asc as compared with 26.6% and 23.3% of patients receiving PEG+Sim. Patient tolerability and safety were similar with both the preparations. According to our data, low-volume PEG+Asc has comparable efficacy, safety, and tolerability as high-volume PEG+Sim; therefore, it can be considered as a good alternative solution for bowel preparation. More improvements are necessary to achieve the target of a perfect preparation.

Allele exchange at the EPSPS locus confers glyphosate tolerance in cassava.

PubMed

Hummel, Aaron W; Chauhan, Raj Deepika; Cermak, Tomas; Mutka, Andrew M; Vijayaraghavan, Anupama; Boyher, Adam; Starker, Colby G; Bart, Rebecca; Voytas, Daniel F; Taylor, Nigel J

2017-12-09

Effective weed control can protect yields of cassava (Manihot esculenta) storage roots. Farmers could benefit from using herbicide with a tolerant cultivar. We applied traditional transgenesis and gene editing to generate robust glyphosate tolerance in cassava. By comparing promoters regulating expression of transformed 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) genes with various paired amino acid substitutions, we found that strong constitutive expression is required to achieve glyphosate tolerance during in vitro selection and in whole cassava plants. Using strategies that exploit homologous recombination (HR) and nonhomologous end-joining (NHEJ) DNA repair pathways, we precisely introduced the best-performing allele into the cassava genome, simultaneously creating a promoter swap and dual amino acid substitutions at the endogenous EPSPS locus. Primary EPSPS-edited plants were phenotypically normal, tolerant to high doses of glyphosate, with some free of detectable T-DNA integrations. Our methods demonstrate an editing strategy for creating glyphosate tolerance in crop plants and demonstrate the potential of gene editing for further improvement of cassava. © 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Effect of Salsalate on Insulin Action, Secretion, and Clearance in Nondiabetic, Insulin-Resistant Individuals: A Randomized, Placebo-Controlled Study

PubMed Central

Liu, Alice; Ariel, Danit; Abbasi, Fahim; Lamendola, Cindy; Grove, Kaylene; Tomasso, Vanessa; Ochoa, Hector; Reaven, Gerald

2014-01-01

OBJECTIVE Salsalate treatment has been shown to improve glucose homeostasis, but the mechanism remains unclear. The aim of this study was to evaluate the effect of salsalate treatment on insulin action, secretion, and clearance rate in nondiabetic individuals with insulin resistance. RESEARCH DESIGN AND METHODS This was a randomized (2:1), single-blind, placebo-controlled study of salsalate (3.5 g daily for 4 weeks) in nondiabetic individuals with insulin resistance. All individuals had measurement of glucose tolerance (75-g oral glucose tolerance test), steady-state plasma glucose (SSPG; insulin suppression test), and insulin secretion and clearance rate (graded-glucose infusion test) before and after treatment. RESULTS Forty-one individuals were randomized to salsalate (n = 27) and placebo (n = 14). One individual from each group discontinued the study. Salsalate improved fasting (% mean change −7% [95% CI −10 to −14] vs. 1% [−3 to 5], P = 0.005) but not postprandial glucose concentration compared with placebo. Salsalate also lowered fasting triglyceride concentration (−25% [−34 to −15] vs. −6% [−26 to 14], P = 0.04). Salsalate had no effect on SSPG concentration or insulin secretion rate but significantly decreased insulin clearance rate compared with placebo (−23% [−30 to −16] vs. 3% [−10 to 15], P < 0.001). Salsalate was well tolerated, but four individuals needed a dose reduction due to symptoms. CONCLUSIONS Salsalate treatment in nondiabetic, insulin-resistant individuals improved fasting, but not postprandial, glucose and triglyceride concentration. These improvements were associated with a decrease in insulin clearance rate without change in insulin action or insulin secretion. PMID:24963111

Micro-instillation of fluorescein with an inoculation loop for ocular surface staining in dry eye syndrome.

PubMed

Courrier, Emilie; Renault, Didier; Kaspi, Mathilde; Marcon, Agathe; Lambert, Victor; Garcin, Thibaud; Chiambaretta, Frederic; Garhofer, Gerhard; Thuret, Gilles; Gain, Philippe

2018-03-01

To describe and validate the micro-instillation of fluorescein on the ocular surface by a disposable calibrated inoculation loop to improve corneal and conjunctival staining quality. Accuracy and precision of the volume of 0.5% sodium fluorescein collected by a single use 1 μl-calibrated inoculation loop were measured using a precision balance. Twenty patients (40 eyes) suffering from dry eye syndrome were enrolled in a prospective interventional nonrandomized study. Fluorescein was instilled with the loop, and slit-lamp images were taken within 30 seconds using cobalt blue light with and without a yellow barrier filter. For comparison, after a washout period, the same images were retaken after instillation of one drop of fluorescein from a single-dose unit. The main outcome measure was the staining quality assessed by three experts, blind to the instillation method. Patient discomfort (tolerance, by a questionnaire) was also compared. The mean volume collected by the loop was 1.18 ± 0.12 μl, compared with 33.70 ± 6.10 μl using the single-dose unit. The loop avoided excess dye responsible for unpleasant tearing, masking of lesions and rapid diffusion into the stroma. Micro-instillation greatly improved image quality without losing information. The yellow filter further improved image contrast. Tolerance was excellent. The 1 μl-calibrated inoculation loop is a safe, convenient, inexpensive, disposable, sterile, well-tolerated tool for reproducible micro-instillation of commercial fluorescein. By greatly improving staining quality, it will help standardize assessment of dry eye severity. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Efficacy and tolerability of a polysaccharide-resin-honey based cough syrup as compared to carbocysteine syrup for children with colds: a randomized, single-blinded, multicenter study.

PubMed

Cohen, Herman Avner; Hoshen, Moshe; Gur, Shmuel; Bahir, Arie; Laks, Yoseph; Blau, Hannah

2017-02-01

Available pediatric treatments for acute cough are limited by lack of demonstrated efficacy. The objective of this trial is to compare the effects of a polysaccharide-resin-honey based cough syrup, and carbocysteine syrups on nocturnal and daytime cough associated with childhood upper respiratory tract infections (URIs). Using a single-blind randomization design, the study recruited children from 4 general pediatric community clinics. Participants included 150 children aged 2 to 5 years with an URI, nocturnal and daytime cough and illness duration of ≤7 days. To be eligible, children had to be free of medication on the day before presentation. A survey was administered to parents on 4 consecutive days beginning from the day of presentation in clinic. Children received the study preparation on the first evening and then 3 times per day for 3 further days. Main outcome measures were cough frequency, cough severity, bothersome nature of cough, and quality of sleep for both child and parent. Both preparations were well tolerated and cough improved over the study period. After one night and on all survey days, there was a significantly better result for polysaccharide-resin-honey (P<0.05) for all the main outcome measures. The trend of improvement over the 4 days was steeper for polysaccharide-resin-honey (P<0.05) with regards to all cough parameters. Both polysaccharide-resin-honey and carbocysteine cough syrups were well tolerated in children over 2 years of age. The polysaccharide-resin-honey syrup was associated with a more rapid and greater improvement in all clinical cough symptoms measured, beginning from the first night of therapy. Both nocturnal and daytime cough improved, as did sleep quality for both children and parents.

The transcriptional regulatory network in the drought response and its crosstalk in abiotic stress responses including drought, cold, and heat.

PubMed

Nakashima, Kazuo; Yamaguchi-Shinozaki, Kazuko; Shinozaki, Kazuo

2014-01-01

Drought negatively impacts plant growth and the productivity of crops around the world. Understanding the molecular mechanisms in the drought response is important for improvement of drought tolerance using molecular techniques. In plants, abscisic acid (ABA) is accumulated under osmotic stress conditions caused by drought, and has a key role in stress responses and tolerance. Comprehensive molecular analyses have shown that ABA regulates the expression of many genes under osmotic stress conditions, and the ABA-responsive element (ABRE) is the major cis-element for ABA-responsive gene expression. Transcription factors (TFs) are master regulators of gene expression. ABRE-binding protein and ABRE-binding factor TFs control gene expression in an ABA-dependent manner. SNF1-related protein kinases 2, group A 2C-type protein phosphatases, and ABA receptors were shown to control the ABA signaling pathway. ABA-independent signaling pathways such as dehydration-responsive element-binding protein TFs and NAC TFs are also involved in stress responses including drought, heat, and cold. Recent studies have suggested that there are interactions between the major ABA signaling pathway and other signaling factors in stress responses. The important roles of these TFs in crosstalk among abiotic stress responses will be discussed. Control of ABA or stress signaling factor expression can improve tolerance to environmental stresses. Recent studies using crops have shown that stress-specific overexpression of TFs improves drought tolerance and grain yield compared with controls in the field.

Co-overexpressing a Plasma Membrane and a Vacuolar Membrane Sodium/Proton Antiporter Significantly Improves Salt Tolerance in Transgenic Arabidopsis Plants

PubMed Central

Pehlivan, Necla; Sun, Li; Jarrett, Philip; Yang, Xiaojie; Mishra, Neelam; Chen, Lin; Kadioglu, Asim; Shen, Guoxin; Zhang, Hong

2016-01-01

The Arabidopsis gene AtNHX1 encodes a vacuolar membrane-bound sodium/proton (Na+/H+) antiporter that transports Na+ into the vacuole and exports H+ into the cytoplasm. The Arabidopsis gene SOS1 encodes a plasma membrane-bound Na+/H+ antiporter that exports Na+ to the extracellular space and imports H+ into the plant cell. Plants rely on these enzymes either to keep Na+ out of the cell or to sequester Na+ into vacuoles to avoid the toxic level of Na+ in the cytoplasm. Overexpression of AtNHX1 or SOS1 could improve salt tolerance in transgenic plants, but the improved salt tolerance is limited. NaCl at concentration >200 mM would kill AtNHX1-overexpressing or SOS1-overexpressing plants. Here it is shown that co-overexpressing AtNHX1 and SOS1 could further improve salt tolerance in transgenic Arabidopsis plants, making transgenic Arabidopsis able to tolerate up to 250 mM NaCl treatment. Furthermore, co-overexpression of AtNHX1 and SOS1 could significantly reduce yield loss caused by the combined stresses of heat and salt, confirming the hypothesis that stacked overexpression of two genes could substantially improve tolerance against multiple stresses. This research serves as a proof of concept for improving salt tolerance in other plants including crops. PMID:26985021

Minimal enteral nutrition to improve adaptation after intestinal resection in piglets and infants

USDA-ARS?s Scientific Manuscript database

Minimal enteral nutrition (MEN) may induce a diet-dependent stimulation of gut adaptation following intestinal resection. Bovine colostrum is rich in growth factors, and we hypothesized that MEN with colostrum would stimulate intestinal adaptation, compared with formula, and would be well tolerated ...

A New Chemotherapeutic Investigation: Piracetam Effects on Dyslexia.

ERIC Educational Resources Information Center

Chase, Christopher H.; Schmitt, R. Larry

1984-01-01

Compared to placebo controls, 28 individuals treated with Piracetam (a new drug thought to enhance learning and memory consolidation) showed statistically significant improvements above baseline scores on measures of effective reading accuracy and comprehension, reading speed, and writing accuracy. The medication was well tolerated and showed no…

Novel drug and soluble target tolerant antidrug antibody assay for therapeutic antibodies bearing the P329G mutation.

PubMed

Wessels, Uwe; Schick, Eginhard; Ritter, Mirko; Kowalewsky, Frank; Heinrich, Julia; Stubenrauch, Kay

2017-06-01

Bridging immunoassays for detection of antidrug antibodies (ADAs) are typically susceptible to high concentrations of residual drug. Sensitive drug-tolerant assays are, therefore, needed. An immune complex assay to detect ADAs against therapeutic antibodies bearing Pro329Gly mutation was established. The assay uses antibodies specific for the Pro329Gly mutation for capture and human soluble Fcγ receptor for detection. When compared with a bridging assay, the new assay showed similar precision, high sensitivity to IgG1 ADA and dramatically improved drug tolerance. However, it was not able to detect early (IgM-based) immune responses. Applied in combination with a bridging assay, the novel assay serves as orthogonal assay for immunogenicity assessment and allows further characterization of ADA responses.

The Yeast HAL1 Gene Improves Salt Tolerance of Transgenic Tomato1

PubMed Central

Gisbert, Carmina; Rus, Ana M.; Bolarín, M. Carmen; López-Coronado, J. Miguel; Arrillaga, Isabel; Montesinos, Consuelo; Caro, Manuel; Serrano, Ramon; Moreno, Vicente

2000-01-01

Overexpression of the HAL1 gene in yeast has a positive effect on salt tolerance by maintaining a high internal K+ concentration and decreasing intracellular Na+ during salt stress. In the present work, the yeast gene HAL1 was introduced into tomato (Lycopersicon esculentum Mill.) by Agrobacterium tumefaciens-mediated transformation. A sample of primary transformants was self-pollinated, and progeny from both transformed and non-transformed plants (controls) were evaluated for salt tolerance in vitro and in vivo. Results from different tests indicated a higher level of salt tolerance in the progeny of two different transgenic plants bearing four copies or one copy of the HAL1 gene. In addition, measurement of the intracellular K+ to Na+ ratios showed that transgenic lines were able to retain more K+ than the control under salt stress. Although plants and yeast cannot be compared in an absolute sense, these results indicate that the mechanism controlling the positive effect of the HAL1 gene on salt tolerance may be similar in transgenic plants and yeast. PMID:10806256

Exploring stress tolerance mechanism of evolved freshwater strain Chlorella sp. S30 under 30 g/L salt.

PubMed

Li, Xuyang; Yuan, Yizhong; Cheng, Dujia; Gao, Juan; Kong, Lingzhao; Zhao, Quanyu; Wei, Wei; Sun, Yuhan

2018-02-01

Enhancement of stress tolerance to high concentration of salt and CO 2 is beneficial for CO 2 capture by microalgae. Adaptive evolution was performed for improving the tolerance of a freshwater strain, Chlorella sp. AE10, to 30 g/L salt. A resulting strain denoted as Chlorella sp. S30 was obtained after 46 cycles (138 days). The stress tolerance mechanism was analyzed by comparative transcriptomic analysis. Although the evolved strain could tolerate 30 g/L salt, high salinity caused loss to photosynthesis, oxidative phosphorylation, fatty acid biosynthesis and tyrosine metabolism. The related genes of antioxidant enzymes, CO 2 fixation, amino acid biosynthesis, central carbon metabolism and ABC transporter proteins were up-regulated. Besides the up-regulation of several genes in Calvin-Benson cycle, they were also identified in C4 photosynthetic pathway and crassulacean acid metabolism pathway. They were essential for the survival and CO 2 fixation of Chlorella sp. S30 under 30 g/L salt and 10% CO 2 . Copyright © 2017 Elsevier Ltd. All rights reserved.

Ectopic expression of phloem motor protein pea forisome PsSEO-F1 enhances salinity stress tolerance in tobacco.

PubMed

Srivastava, Vineet Kumar; Raikwar, Shailendra; Tuteja, Renu; Tuteja, Narendra

2016-05-01

PsSEOF-1 binds to calcium and its expression is upregulated by salinity treatment. PsSEOF - 1 -overexpressing transgenic tobacco showed enhanced salinity stress tolerance by maintaining cellular ion homeostasis and modulating ROS-scavenging pathway. Calcium (Ca(2+)) plays important role in growth, development and stress tolerance in plants. Cellular Ca(2+) homeostasis is achieved by the collective action of channels, pumps, antiporters and by Ca(2+) chelators present in the cell like calcium-binding proteins. Forisomes are ATP-independent mechanically active motor proteins known to function in wound sealing of injured sieve elements of phloem tissue. The Ca(2+)-binding activity of forisome and its role in abiotic stress signaling were largely unknown. Here we report the Ca(2+)-binding activity of pea forisome (PsSEO-F1) and its novel function in promoting salinity tolerance in transgenic tobacco. Native PsSEO-F1 promoter positively responded in salinity stress as confirmed using GUS reporter. Overexpression of PsSEO-F1 tobacco plants confers salinity tolerance by alleviating ionic toxicity and increased ROS scavenging activity which probably results in reduced membrane damage and improved yield under salinity stress. Evaluation of several physiological indices shows an increase in relative water content, electrolyte leakage, proline accumulation and chlorophyll content in transgenic lines as compared with null-segregant control. Expression of several genes involved in cellular homeostasis is perturbed by PsSEO-F1 overexpression. These findings suggest that PsSEO-F1 provides salinity tolerance through cellular Ca(2+) homeostasis which in turn modulates ROS machinery providing indirect link between Ca(2+) and ROS signaling under salinity-induced perturbation. PsSEO-F1 most likely functions in salinity stress tolerance by improving antioxidant machinery and mitigating ion toxicity in transgenic lines. This finding should make an important contribution in our better understanding of the significance of calcium signaling in phloem tissue leading to salinity stress tolerance.

Whey protein isolate improves acid and bile tolerances of Streptococcus thermophilus ST-M5 and Lactobacillus delbrueckii ssp. bulgaricus LB-12.

PubMed

Vargas, Luis A; Olson, Douglas W; Aryana, Kayanush J

2015-04-01

Acid tolerance and bile tolerance are important probiotic characteristics. Whey proteins contain branched-chain amino acids, which play a role in muscle building and are popular among athletes. Increasing emphasis is being placed on diets containing less carbohydrate, less fat, and more protein. The effect of incremental additions of whey protein isolate (WPI) on probiotic characteristics of pure cultures is not known. The objective of this study was to determine the influence of added WPI on acid tolerance and bile tolerance of pure cultures of Streptococcus thermophilus ST-M5 and Lactobacillus bulgaricus LB-12. The WPI was used at 0 (control), 1, 2 and 3% (wt/vol). Assessment of acid tolerance was conducted on pure cultures at 30-min intervals for 2h of acid exposure and bile tolerance at 1-h intervals for 5h of bile exposure. Use of 1, 2, and 3% WPI improved acid tolerance of Strep. thermophilus ST-M5 and Lb. bulgaricus LB-12. The highest counts for acid tolerance of Strep. thermophilus ST-M5 and Lb. bulgaricus LB-12 were obtained when 3% WPI was used. Use of 2 and 3% WPI improved bile tolerance of Strep. thermophilus ST-M5 and Lb. bulgaricus LB-12 over 5h of bile exposure. The use of WPI is recommended to improve acid and bile tolerance of the yogurt culture bacteria Strep. thermophilus ST-M5 and Lb. bulgaricus LB-12. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Engineering improved bio-jet fuel tolerance in Escherichia coli using a transgenic library from the hydrocarbon-degrader Marinobacter aquaeolei.

PubMed

Tomko, Timothy A; Dunlop, Mary J

2015-01-01

Recent metabolic engineering efforts have generated microorganisms that can produce biofuels, including bio-jet fuels, however these fuels are often toxic to cells, limiting production yields. There are natural examples of microorganisms that have evolved mechanisms for tolerating hydrocarbon-rich environments, such as those that thrive near natural oil seeps and in oil-polluted waters. Using genomic DNA from the hydrocarbon-degrading microbe Marinobacter aquaeolei, we constructed a transgenic library that we expressed in Escherichia coli. We exposed cells to inhibitory levels of pinene, a monoterpene that can serve as a jet fuel precursor with chemical properties similar to existing tactical fuels. Using a sequential strategy with a fosmid library followed by a plasmid library, we were able to isolate a region of DNA from the M. aquaeolei genome that conferred pinene tolerance when expressed in E. coli. We determined that a single gene, yceI, was responsible for the tolerance improvements. Overexpression of this gene placed no additional burden on the host. We also tested tolerance to other monoterpenes and showed that yceI selectively improves tolerance. The genomes of hydrocarbon-tolerant microbes represent a rich resource for tolerance engineering. Using a transgenic library, we were able to identify a single gene that improves E. coli's tolerance to the bio-jet fuel precursor pinene.

Tolerance engineering in bacteria for the production of advanced biofuels and chemicals.

PubMed

Mukhopadhyay, Aindrila

2015-08-01

During microbial production of solvent-like compounds, such as advanced biofuels and bulk chemicals, accumulation of the final product can negatively impact the cultivation of the host microbe and limit the production levels. Consequently, improving solvent tolerance is becoming an essential aspect of engineering microbial production strains. Mechanisms ranging from chaperones to transcriptional factors have been used to obtain solvent-tolerant strains. However, alleviating growth inhibition does not invariably result in increased production. Transporters specifically have emerged as a powerful category of proteins that bestow tolerance and often improve production but are difficult targets for cellular expression. Here we review strain engineering, primarily as it pertains to bacterial solvent tolerance, and the benefits and challenges associated with the expression of membrane-localized transporters in improving solvent tolerance and production. Copyright © 2015 Elsevier Ltd. All rights reserved.

Overexpression of HARDY, an AP2/ERF gene from Arabidopsis, improves drought and salt tolerance by reducing transpiration and sodium uptake in transgenic Trifolium alexandrinum L.

PubMed

Abogadallah, Gaber M; Nada, Reham M; Malinowski, Robert; Quick, Paul

2011-06-01

Trifolium alexandrinum L. was transformed with the Arabidopsis HARDY gene that belongs to the stress-related AP2/ERF (APETALA2/ethylene responsive element binding factors) superfamily of transcription factors. The fresh weights of the transgenic lines L2 and L3 were improved by 42 and 55% under drought stress and by 38 and 95% under salt stress compared to the wild type, respectively. The dry weights were similarly improved. Overexpression of HARDY improved the instantaneous water use efficiency (WUE) under drought stress by reducing transpiration (E) and under salt stress by improving photosynthesis (A), through reducing Na+ accumulation in leaves, and reducing E. However, HARDY improved the growth of drought-stressed transgenic plants as compared to the wild type by delaying water depletion from soil and preventing rapid decline in A. L2 and L3 had thicker stems and in case of L3, more xylem rows per vascular bundle, which may have made L3 more resistant to lodging in the field. Field performance of L2 and L3 under combined drought and salt stress was significantly better than that of the wild type in terms of fresh and dry weights (40%, 46% and 31%, 40%, respectively). The results provide further evidence for the efficiency of overexpression of a single gene in improving tolerance to abiotic stress under field conditions.

Some low homogenization pressures improve certain probiotic characteristics of yogurt culture bacteria and Lactobacillus acidophilus LA-K.

PubMed

Muramalla, T; Aryana, K J

2011-08-01

Lactobacillus delbrueckii ssp. bulgaricus, Streptococcus salivarius ssp. thermophilus, and Lactobacillus acidophilus are dairy cultures widely used in the manufacture of cultured dairy products. Commonly used homogenization pressures in the dairy industry are 13.80 MPa or less. It is not known whether low homogenization pressures can stimulate bacteria to improve their probiotic characteristics. Objectives were to determine the effect of homogenization at 0, 3.45, 6.90, 10.34, and 13.80 MPa on acid tolerance, bile tolerance, protease activity, and growth of L. delbrueckii ssp. bulgaricus LB-12, S. salivarius ssp. thermophilus ST-M5, and L. acidophilus LA-K. The cultures were individually inoculated in cool autoclaved skim milk (4°C) and homogenized for 5 continuous passes. Growth and bile tolerance of samples were determined hourly for 10h of incubation. Acid tolerance was determined every 20 min for 120 min of incubation. Protease activity was determined at 0, 12, and 24h of incubation. All homogenization pressures studied improved acid tolerance of L. delbrueckii ssp. bulgaricus LB-12 but had no beneficial effect on protease activity and had negative effects on growth and bile tolerance. A pressure of 6.90 MPa improved acid tolerance, bile tolerance, and protease activity of S. salivarius ssp. thermophilus ST-M5, but none of the homogenization pressures studied had an effect on its growth. Homogenization pressures of 13.80 and 6.90 MPa improved acid tolerance and bile tolerance, respectively, of L. acidophilus LA-K but had no effect on protease activity and its growth. Some low homogenization pressures positively influenced some characteristics of yogurt culture bacteria and L. acidophilus LA-K. Culture pretreatment with some low homogenization pressures can be recommended for improvement of certain probiotic characteristics. Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Six-minute stepper test: a valid clinical exercise tolerance test for COPD patients

PubMed Central

Grosbois, JM; Riquier, C; Chehere, B; Coquart, J; Béhal, H; Bart, F; Wallaert, B; Chenivesse, C

2016-01-01

Introduction Exercise tolerance testing is an integral part of the pulmonary rehabilitation (PR) management of patients with chronic obstructive pulmonary disease (COPD). The 6-minute stepper test (6MST) is a new, well-tolerated, reproducible exercise test, which can be performed without any spatial constraints. Objective The aim of this study was to compare the results of the 6MST to those obtained during a 6-minute walk test (6MWT) and cardiopulmonary exercise testing (CPET) in a cohort of COPD patients. Methods Ninety-one COPD patients managed by outpatient PR and assessed by 6MST, 6MWT, and CPET were retrospectively included in this study. Correlations between the number of steps on the 6MST, the distance covered on the 6MWT, oxygen consumption, and power at the ventilatory threshold and at maximum effort during CPET were analyzed before starting PR, and the improvement on the 6MST and 6MWT was compared after PR. Results The number of steps on the 6MST was significantly correlated with the distance covered on the 6MWT (r=0.56; P<0.0001), the power at maximum effort (r=0.46; P<0.0001), and oxygen consumption at maximum effort (r=0.39; P<0.005). Performances on the 6MST and 6MWT were significantly improved after PR (570 vs 488 steps, P=0.001 and 448 vs 406 m, respectively; P<0.0001). Improvements of the 6MST and 6MWT after PR were significantly correlated (r=0.34; P=0.03). Conclusion The results of this study show that the 6MST is a valid test to evaluate exercise tolerance in COPD patients. The use of this test in clinical practice appears to be particularly relevant for the assessment of patients managed by home PR. PMID:27099483

ALA Pretreatment Improves Waterlogging Tolerance of Fig Plants

PubMed Central

An, Yuyan; Qi, Lin; Wang, Liangju

2016-01-01

5-aminolevulinic acid (ALA), a natural and environmentally friendly plant growth regulator, can improve plant tolerance to various environmental stresses. However, whether ALA can improve plant waterlogging tolerance is unknown. Here, we investigated the effects of ALA pretreatment on the waterlogging-induced damage of fig (Ficus carica Linn.) plants, which often suffer from waterlogging stress. ALA pretreatment significantly alleviated stress-induced morphological damage, increased leaf relative water content (RWC), and reduced leaf superoxide anion (O2⋅¯) production rate and malonaldehyde (MDA) content in fig leaves, indicating ALA mitigates waterlogging stress of fig plants. We further demonstrated that ALA pretreatment largely promoted leaf chlorophyll content, photosynthetic electron transfer ability, and photosynthetic performance index, indicating ALA significantly improves plant photosynthetic efficiency under waterlogging stress. Moreover, ALA pretreatment significantly increased activities of leaf superoxide dismutase (SOD) and peroxidase (POD), root vigor, and activities of root alcohol dehydrogenase (ADH), and lactate dehydrogenase (LDH), indicating ALA also significantly improves antioxidant ability and root function of fig plants under waterlogging stress. Taken together, ALA pretreatment improves waterlogging tolerance of fig plants significantly, and the promoted root respiration, leaf photosynthesis, and antioxidant ability may contribute greatly to this improvement. Our data firstly shows that ALA can improve plant waterlogging tolerance. PMID:26789407

Combined transcranial direct current stimulation and home-based occupational therapy for upper limb motor impairment following intracerebral hemorrhage: a double-blind randomized controlled trial.

PubMed

Mortensen, Jesper; Figlewski, Krystian; Andersen, Henning

2016-01-01

To investigate the combined effect of transcranial direct current stimulation (tDCS) and home-based occupational therapy on activities of daily living (ADL) and grip strength, in patients with upper limb motor impairment following intracerebral hemorrhage (ICH). A double-blind randomized controlled trial with one-week follow-up. Patients received five consecutive days of occupational therapy at home, combined with either anodal (n = 8) or sham (n = 7) tDCS. The primary outcome was ADL performance, which was assessed with the Jebsen-Taylor test (JTT). Both groups improved JTT over time (p < 0.01). The anodal group improved grip strength compared with the sham group from baseline to post-assessment (p = 0.025). However, this difference was attenuated at one-week follow-up. There was a non-significant tendency for greater improvement in JTT in the anodal group compared with the sham group, from baseline to post-assessment (p = 0.158). Five consecutive days of tDCS combined with occupational therapy provided greater improvements in grip strength compared with occupational therapy alone. tDCS is a promising add-on intervention regarding training of upper limb motor impairment. It is well tolerated by patients and can easily be applied for home-based training. Larger studies with long-term follow-up are needed to further explore possible effects of tDCS in patients with ICH. Five consecutive days of tDCS combined with occupational therapy provided greater improvements in grip strength compared with occupational therapy alone. tDCS is well tolerated by patients and can easily be applied for home-based rehabilitation.

Improvement of tolerance to freeze-thaw stress of baker's yeast by cultivation with soy peptides.

PubMed

Izawa, Shingo; Ikeda, Kayo; Takahashi, Nobuyuki; Inoue, Yoshiharu

2007-06-01

The tolerance to freeze-thaw stress of yeast cells is critical for frozen-dough technology in the baking industry. In this study, we examined the effects of soy peptides on the freeze-thaw stress tolerance of yeast cells. We found that the cells cultured with soy peptides acquired improved tolerance to freeze-thaw stress and retained high leavening ability in dough after frozen storage for 7 days. The final quality of bread regarding its volume and texture was also improved by using yeast cells cultured with soy peptides. These findings promote the utilization of soy peptides as ingredients of culture media to improve the quality of baker's yeast.

Ablation of Neurons Expressing Melanin-Concentrating Hormone (MCH) in Adult Mice Improves Glucose Tolerance Independent of MCH Signaling

PubMed Central

Whiddon, Benjamin B.; Palmiter, Richard D.

2013-01-01

Melanin-concentrating hormone (MCH)-expressing neurons have been ascribed many roles based on tudies of MCH-deficient mice. However, MCH neurons express other neurotransmitters, including GABA, nesfatin, and cocaine–amphetamine-regulated transcript. The importance of these other signaling molecules made by MCH neurons remains incompletely characterized. To determine the roles of MCH neurons in vivo, we targeted expression of the human diphtheria toxin receptor (DTR) to the gene for MCH (Pmch). Within 2 weeks of diphtheria toxin injection, heterozygous PmchDTR/+ mice lost 98% of their MCH neurons. These mice became lean but ate normally and were hyperactive, especially during a fast. They also responded abnormally to psychostimulants. For these phenotypes, ablation of MCH neurons recapitulated knock-out of MCH, so MCH appears to be the critical neuromodulator released by these neurons. In contrast, MCH-neuron-ablated mice showed improved glucose tolerance when compared with MCH-deficient mutant mice and wild-type mice. We conclude that MCH neurons regulate glucose tolerance through signaling molecules other than MCH. PMID:23365238

Identification of Abiotic Stress Protein Biomarkers by Proteomic Screening of Crop Cultivar Diversity

PubMed Central

Barkla, Bronwyn J.

2016-01-01

Modern day agriculture practice is narrowing the genetic diversity in our food supply. This may compromise the ability to obtain high yield under extreme climactic conditions, threatening food security for a rapidly growing world population. To identify genetic diversity, tolerance mechanisms of cultivars, landraces and wild relatives of major crops can be identified and ultimately exploited for yield improvement. Quantitative proteomics allows for the identification of proteins that may contribute to tolerance mechanisms by directly comparing protein abundance under stress conditions between genotypes differing in their stress responses. In this review, a summary is provided of the data accumulated from quantitative proteomic comparisons of crop genotypes/cultivars which present different stress tolerance responses when exposed to various abiotic stress conditions, including drought, salinity, high/low temperature, nutrient deficiency and UV-B irradiation. This field of research aims to identify molecular features that can be developed as biomarkers for crop improvement, however without accurate phenotyping, careful experimental design, statistical robustness and appropriate biomarker validation and verification it will be challenging to deliver what is promised. PMID:28248236

Identification of Abiotic Stress Protein Biomarkers by Proteomic Screening of Crop Cultivar Diversity.

PubMed

Barkla, Bronwyn J

2016-09-08

Modern day agriculture practice is narrowing the genetic diversity in our food supply. This may compromise the ability to obtain high yield under extreme climactic conditions, threatening food security for a rapidly growing world population. To identify genetic diversity, tolerance mechanisms of cultivars, landraces and wild relatives of major crops can be identified and ultimately exploited for yield improvement. Quantitative proteomics allows for the identification of proteins that may contribute to tolerance mechanisms by directly comparing protein abundance under stress conditions between genotypes differing in their stress responses. In this review, a summary is provided of the data accumulated from quantitative proteomic comparisons of crop genotypes/cultivars which present different stress tolerance responses when exposed to various abiotic stress conditions, including drought, salinity, high/low temperature, nutrient deficiency and UV-B irradiation. This field of research aims to identify molecular features that can be developed as biomarkers for crop improvement, however without accurate phenotyping, careful experimental design, statistical robustness and appropriate biomarker validation and verification it will be challenging to deliver what is promised.

Ablation of neurons expressing melanin-concentrating hormone (MCH) in adult mice improves glucose tolerance independent of MCH signaling.

PubMed

Whiddon, Benjamin B; Palmiter, Richard D

2013-01-30

Melanin-concentrating hormone (MCH)-expressing neurons have been ascribed many roles based on studies of MCH-deficient mice. However, MCH neurons express other neurotransmitters, including GABA, nesfatin, and cocaine-amphetamine-regulated transcript. The importance of these other signaling molecules made by MCH neurons remains incompletely characterized. To determine the roles of MCH neurons in vivo, we targeted expression of the human diphtheria toxin receptor (DTR) to the gene for MCH (Pmch). Within 2 weeks of diphtheria toxin injection, heterozygous Pmch(DTR/+) mice lost 98% of their MCH neurons. These mice became lean but ate normally and were hyperactive, especially during a fast. They also responded abnormally to psychostimulants. For these phenotypes, ablation of MCH neurons recapitulated knock-out of MCH, so MCH appears to be the critical neuromodulator released by these neurons. In contrast, MCH-neuron-ablated mice showed improved glucose tolerance when compared with MCH-deficient mutant mice and wild-type mice. We conclude that MCH neurons regulate glucose tolerance through signaling molecules other than MCH.

Down-Regulating α-Galactosidase Enhances Freezing Tolerance in Transgenic Petunia1

PubMed Central

Pennycooke, Joyce C.; Jones, Michelle L.; Stushnoff, Cecil

2003-01-01

α-Galactosidase (α-Gal; EC 3.2.1.22) is involved in many aspects of plant metabolism, including hydrolysis of the α-1,6 linkage of raffinose oligosaccharides during deacclimation. To examine the relationship between endogenous sugars and freezing stress, the expression of α-Gal was modified in transgenic petunia (Petunia × hybrida cv Mitchell). The tomato (Lycopersicon esculentum) Lea-Gal gene under the control of the Figwort Mosaic Virus promoter was introduced into petunia in the sense and antisense orientations using Agrobacterium tumefaciens-mediated transformation. RNA gel blots confirmed that α-Gal transcripts were reduced in antisense lines compared with wild type, whereas sense plants had increased accumulation of α-Gal mRNAs. α-Gal activity followed a similar trend, with reduced activity in antisense lines and increased activity in all sense lines evaluated. Raffinose content of nonacclimated antisense plants increased 12- to 22-fold compared with wild type, and 22- to 53-fold after cold acclimation. Based upon electrolyte leakage tests, freezing tolerance of the antisense lines increased from –4°C for cold-acclimated wild-type plants to –8°C for the most tolerant antisense line. Down-regulating α-Gal in petunia results in an increase in freezing tolerance at the whole-plant level in nonacclimated and cold-acclimated plants, whereas overexpression of the α-Gal gene caused a decrease in endogenous raffinose and impaired freezing tolerance. These results suggest that engineering raffinose metabolism by transformation with α-Gal provides an additional method for improving the freezing tolerance of plants. PMID:14500789

Improved clinical tolerance to chronic lactose ingestion in subjects with lactose intolerance: a placebo effect?

PubMed Central

Briet, F; Pochart, P; Marteau, P; Flourie, B; Arrigoni, E; Rambaud, J

1997-01-01

Background—Uncontrolled studies of lactose intolerant subjects have shown that symptom severity decreases after chronic lactose consumption. Adaptation of the colonic flora might explain this improvement. 
Aims—To compare the effects of regular administration of either lactose or sucrose on clinical tolerance and bacterial adaptation to lactose. 
Methods—Forty six lactose intolerant subjects underwent two 50 g lactose challenges on days 1 and 15. Between these days they were given 34 g of lactose or sucrose per day, in a double blind protocol. Stool samples were obtained on days 0 and 14, to measure faecal β-galactosidase and pH. Symptoms, breath H2 excretion, faecal weight and electrolytes, and orofaecal transit time were assessed. 
Results—Except for faecal weight, symptoms were significantly milder during the second challenge in both groups, and covariance analysis showed no statistical difference between them. In the lactose group, but not in the sucrose group, faecal β-galactosidase activity increased, pH dropped, and breath H2 excretion decreased. 
Conclusion—Bacterial adaptation occurred when lactose intolerant subjects ingested lactose for 13 days, and all symptoms except diarrhoea regressed. Clinical improvement was also observed in the control group which displayed no signs of metabolic adaptation. This suggests that improved clinical tolerance may be just a placebo effect. 

 Keywords: lactose; lactose intolerance; colonic adaptation; lactase deficiency PMID:9414969

Selecting Native Arbuscular Mycorrhizal Fungi to Promote Cassava Growth and Increase Yield under Field Conditions

PubMed Central

Séry, D. Jean-Marc; Kouadjo, Z. G. Claude; Voko, B. R. Rodrigue; Zézé, Adolphe

2016-01-01

The use of arbuscular mycorrhizal fungal (AMF) inoculation in sustainable agriculture is now widespread worldwide. Although the use of inoculants consisting of native AMF is highly recommended as an alternative to commercial ones, there is no strategy to allow the selection of efficient fungal species from natural communities. The objective of this study was (i) to select efficient native AMF species (ii) evaluate their impact on nematode and water stresses, and (iii) evaluate their impact on cassava yield, an important food security crop in tropical and subtropical regions. Firstly, native AMF communities associated with cassava rhizospheres in fields were collected from different areas and 7 AMF species were selected, based upon their ubiquity and abundance. Using these criteria, two morphotypes (LBVM01 and LBVM02) out of the seven AMF species selected were persistently dominant when cassava was used as a trap plant. LBVM01 and LBVM02 were identified as Acaulospora colombiana (most abundant) and Ambispora appendicula, respectively, after phylogenetic analyses of LSU-ITS-SSU PCR amplified products. Secondly, the potential of these two native AMF species to promote growth and enhance tolerance to root-knot nematode and water stresses of cassava (Yavo variety) was evaluated using single and dual inoculation in greenhouse conditions. Of the two AMF species, it was shown that A. colombiana significantly improved the growth of the cassava and enhanced tolerance to water stress. However, both A. colombiana and A. appendicula conferred bioprotective effects to cassava plants against the nematode Meloidogyne spp., ranging from resistance (suppression or reduction of the nematode reproduction) or tolerance (low or no suppression in cassava growth). Thirdly, the potential of these selected native AMF to improve cassava growth and yield was evaluated under field conditions, compared to a commercial inoculant. In these conditions, the A. colombiana single inoculation and the dual inoculation significantly improved cassava yield compared to the commercial inoculant. This is the first report on native AMF species exhibiting multiple benefits for cassava crop productivity, namely improved plant growth and yield, water stress tolerance and nematode resistance. PMID:28066381

Tolerability and effects on quality of life of liposomal nasal spray treatment compared to nasal ointment containing dexpanthenol or isotonic NaCl spray in patients with rhinitis sicca.

PubMed

Hahn, C; Böhm, M; Allekotte, S; Mösges, R

2013-09-01

This study aimed to investigate symptom reduction via the liposomal nasal spray LipoNasal (LN) in patients with rhinitis sicca. Tolerability and the impact on quality of life were also examined. The same parameters were established in parallel for treatment approaches with Bepanthen (BP) nasal ointment containing dexpanthenol and the Rhinomer (RH) nasal spray containing NaCl. This prospective, controlled, open-label observation study was a multicenter trial. 92 patients with rhinitis sicca were allocated to three arms according to their symptoms: LN: n = 33; BP: n = 32 and RH: n = 27. The study comprised three visits at an interval of 14 days. Efficacy was examined by the Rhinitis Sicca Symptom Score (RSSS) documented daily and at the visits based on an endoscopic evaluation. The nasal spray sensory scale was used to investigate the tolerability. Quality of life (QoL) was measured by means of the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) and the "Short Form 12" of the "Impact on Health-Related Quality of Life (HRQL)" questionnaire on general quality of life. Nasal symptoms improved significantly (p = 0.001) under all three treatment approaches, reflected by the reduction in the RSSS and the Endoscopy Sum Score. A comparison of the three groups showed that no therapy was significantly superior to any of the others (p = 0.410). The tolerability of all treatments was good. Concerning the nasal moisturization, LipoNasal was evaluated better than Bepanthen and Rhinomer. Quality of life improved in all groups, but not significantly. The results show good efficacy and tolerability of the liposomal nasal spray compared to generally recognized treatments of rhinitis sicca with dexpanthenol nasal ointment and NaCl nasal spray. LipoNasal therefore constitutes a good treatment for patients suffering from dry nose.

Comparative analysis of root transcriptomes from two contrasting drought-responsive Williams 82 and DT2008 soybean cultivars under normal and dehydration conditions

PubMed Central

Ha, Chien Van; Watanabe, Yasuko; Tran, Uyen Thi; Le, Dung Tien; Tanaka, Maho; Nguyen, Kien Huu; Seki, Motoaki; Nguyen, Dong Van; Tran, Lam-Son Phan

2015-01-01

The economically important DT2008 and the model Williams 82 (W82) soybean cultivars were reported to have differential drought-tolerant degree to dehydration and drought, which was associated with root trait. Here, we used 66K Affymetrix Soybean Array GeneChip to compare the root transcriptomes of DT2008 and W82 seedlings under normal, as well as mild (2 h treatment) and severe (10 h treatment) dehydration conditions. Out of the 38172 soybean genes annotated with high confidence, 822 (2.15%) and 632 (1.66%) genes showed altered expression by dehydration in W82 and DT2008 roots, respectively, suggesting that a larger machinery is required to be activated in the drought-sensitive W82 cultivar to cope with the stress. We also observed that long-term dehydration period induced expression change of more genes in soybean roots than the short-term one, independently of the genotypes. Furthermore, our data suggest that the higher drought tolerability of DT2008 might be attributed to the higher number of genes induced in DT2008 roots than in W82 roots by early dehydration, and to the expression changes of more genes triggered by short-term dehydration than those by prolonged dehydration in DT2008 roots vs. W82 roots. Differentially expressed genes (DEGs) that could be predicted to have a known function were further analyzed to gain a basic understanding on how soybean plants respond to dehydration for their survival. The higher drought tolerability of DT2008 vs. W82 might be attributed to differential expression in genes encoding osmoprotectant biosynthesis-, detoxification- or cell wall-related proteins, kinases, transcription factors and phosphatase 2C proteins. This research allowed us to identify genetic components that contribute to the improved drought tolerance of DT2008, as well as provide a useful genetic resource for in-depth functional analyses that ultimately leads to development of soybean cultivars with improved tolerance to drought. PMID:26300889

Comparison of preservative-free ketotifen fumarate and preserved olopatadine hydrochloride eye drops in the treatment of moderate to severe seasonal allergic conjunctivitis.

PubMed

Mortemousque, B; Bourcier, T; Khairallah, M; Messaoud, R; Brignole-Baudouin, F; Renault, D; Rebika, H; Brémond-Gignac, D

2014-01-01

To compare preservative-free ketotifen 0.025% ophthalmic solution to olopatadine 0.1% ophthalmic solution in with the treatment of seasonal allergic conjunctivitis (SAC) in clinical practice. This was a comparative, randomised, investigator-masked, pilot clinical study in adult patients with documented history of SAC and presenting with moderate to severe itching and conjunctival hyperemia. Eligible patients initiated either ketotifen or olopatadine treatment at a dose of one drop twice daily for 28days. The resolution of ocular signs and symptoms was assessed on day 7 and day 28. Itching was also assessed within 15minutes following the first instillation (day 0). Conjunctival impression cytology was performed at each visit to assess the evolution of ICAM-1 expression (day 0, 7 and 28). Seventy-five patients were randomised (ketotifen: 38 patients; olopatadine: 37 patients). At day 28, the composite score for primary criteria (itching, tearing, and conjunctival hyperemia) improved from 6.8±1.2 to 0.9±1.0 in the Ketotifen group, without statistically significant difference between treatment groups (P=0.67). There was no relevant difference between treatment groups in other efficacy parameters, except a trend for a more rapid resolution of conjunctival hyperemia in the Ketotifen group. Both drugs were well tolerated, with a trend for a better tolerability reported by patients on ketotifen compared to those on olopatadine at day 7 (P=0.054). A rapid and comparable improvement in SAC was achieved after 28days of treatment with both preservative-free ketotifen and preserved olopatadine ophthalmic solutions, with a slightly better ocular tolerance with unpreserved ketotifen 0.025% eye drops. Copyright © 2013. Published by Elsevier Masson SAS.

Valsartan Improves β-Cell Function and Insulin Sensitivity in Subjects With Impaired Glucose Metabolism

PubMed Central

van der Zijl, Nynke J.; Moors, Chantalle C.M.; Goossens, Gijs H.; Hermans, Marc M.H.; Blaak, Ellen E.; Diamant, Michaela

2011-01-01

OBJECTIVE Recently, the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research Trial demonstrated that treatment with the angiotensin receptor blocker (ARB) valsartan for 5 years resulted in a relative reduction of 14% in the incidence of type 2 diabetes in subjects with impaired glucose metabolism (IGM). We investigated whether improvements in β-cell function and/or insulin sensitivity underlie these preventive effects of the ARB valsartan in the onset of type 2 diabetes. RESEARCH DESIGN AND METHODS In this randomized controlled, double-blind, two-center study, the effects of 26 weeks of valsartan (320 mg daily; n = 40) or placebo (n = 39) on β-cell function and insulin sensitivity were assessed in subjects with impaired fasting glucose and/or impaired glucose tolerance, using a combined hyperinsulinemic-euglycemic and hyperglycemic clamp with subsequent arginine stimulation and a 2-h 75-g oral glucose tolerance test (OGTT). Treatment effects were analyzed using ANCOVA, adjusting for center, glucometabolic status, and sex. RESULTS Valsartan increased first-phase (P = 0.028) and second-phase (P = 0.002) glucose-stimulated insulin secretion compared with placebo, whereas the enhanced arginine-stimulated insulin secretion was comparable between groups (P = 0.25). In addition, valsartan increased the OGTT-derived insulinogenic index (representing first-phase insulin secretion after an oral glucose load; P = 0.027). Clamp-derived insulin sensitivity was significantly increased with valsartan compared with placebo (P = 0.049). Valsartan treatment significantly decreased systolic and diastolic blood pressure compared with placebo (P < 0.001). BMI remained unchanged in both treatment groups (P = 0.89). CONCLUSIONS Twenty-six weeks of valsartan treatment increased glucose-stimulated insulin release and insulin sensitivity in normotensive subjects with IGM. These findings may partly explain the beneficial effects of valsartan in the reduced incidence of type 2 diabetes. PMID:21330640

Preclinical safety profile of trastuzumab emtansine (T-DM1): Mechanism of action of its cytotoxic component retained with improved tolerability

DOE Office of Scientific and Technical Information (OSTI.GOV)

Poon, Kirsten Achilles, E-mail: achilles.kirsten@gene.com; Flagella, Kelly; Beyer, Joseph

2013-12-01

Trastuzumab emtansine (T-DM1) is the first antibody-drug conjugate (ADC) approved for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. The therapeutic premise of ADCs is based on the hypothesis that targeted delivery of potent cytotoxic drugs to tumors will provide better tolerability and efficacy compared with non-targeted delivery, where poor tolerability can limit efficacious doses. Here, we present results from preclinical studies characterizing the toxicity profile of T-DM1, including limited assessment of unconjugated DM1. T-DM1 binds primate ErbB2 and human HER2 but not the rodent homolog c-neu. Therefore, antigen-dependent and non-antigen-dependent toxicity was evaluated in monkeysmore » and rats, respectively, in both single- and repeat-dose studies; toxicity of DM1 was assessed in rats only. T-DM1 was well tolerated at doses up to 40 mg/kg (∼ 4400 μg DM1/m{sup 2}) and 30 mg/kg (∼ 6000 μg DM1/m{sup 2}) in rats and monkeys, respectively. In contrast, DM1 was only tolerated up to 0.2 mg/kg (1600 μg DM1/m{sup 2}). This suggests that at least two-fold higher doses of the cytotoxic agent are tolerated in T-DM1, supporting the premise of ADCs to improve the therapeutic index. In addition, T-DM1 and DM1 safety profiles were similar and consistent with the mechanism of action of DM1 (i.e., microtubule disruption). Findings included hepatic, bone marrow/hematologic (primarily platelet), lymphoid organ, and neuronal toxicities, and increased numbers of cells of epithelial and phagocytic origin in metaphase arrest. These adverse effects did not worsen with chronic dosing in monkeys and are consistent with those reported in T-DM1-treated patients to date. - Highlights: • T-DM1 was well tolerated in preclinical studies in rats and cynomolgus monkeys. • T-DM1 is associated with bone marrow/hematologic, hepatic, and neuronal toxicities. • T-DM1 toxicities are related to DM1 mechanisms of action and pharmacologic activity. • When conjugated in T-DM1, higher doses of DM1 can be tolerated. • Antibody-drug conjugates may improve the therapeutic window for cytotoxic agents.« less

[Effects of dietary fiber on the glucose tolerance in spontaneously diabetic rats--comparison among barley, rice, and corn starch].

PubMed

Li, Jue; Kaneko, Takashi; Wang, Yuan; Qin, Li-Qiang; Sato, Akio

2003-05-01

In this study, the effects of a barley diet containing high dietary fiber on the onset and development of diabetes mellitus in spontaneously diabetic rats was investigated by comparing with a rice diet containing low dietary fiber and an alpha-corn starch diet containing very low dietary fiber. 30 male Goto-Kakizaki (GK) strain rats (8 weeks of age) were randomly assigned to 3 groups; high barley (HB) group on a barley diet (dietary fiber intake, 1.79 g/day/rat), rice (R) group on a rice diet (dietary fiber intake, 0.46 g/day/rat), and alpha-corn starch (CS) group on an alpha-corn starch diet (dietary fiber intake, 0.24 g/day/rat). The carbohydrate (70%), fat (10%), and protein (20%) contents of these 3 diets were equal, and the rats were pair-fed each diet for 3 months. Feeding for 3 months showed that fasting plasma glucose level in the HB group was significantly lower than in the R and CS groups; the glucose tolerance in the HB group was markedly improved. Moreover, the plasma cholesterol and triglyceride levels in the HB group were significantly lower than those of the R and CS groups. Our findings demonstrated that barley enabled glycemic control and improved glucose tolerance compared with rice or alpha-corn starch.

Enhance nisin yield via improving acid-tolerant capability of Lactococcus lactis F44.

PubMed

Zhang, Jian; Caiyin, Qinggele; Feng, Wenjing; Zhao, Xiuli; Qiao, Bin; Zhao, Guangrong; Qiao, Jianjun

2016-06-16

Traditionally, nisin was produced industrially by using Lactococcus lactis in the neutral fermentation process. However, nisin showed higher activity in the acidic environment. How to balance the pH value for bacterial normal growth and nisin activity might be the key problem. In this study, 17 acid-tolerant genes and 6 lactic acid synthetic genes were introduced in L. lactis F44, respectively. Comparing to the 2810 IU/mL nisin yield of the original strain F44, the nisin titer of the engineered strains over-expressing hdeAB, ldh and murG, increased to 3850, 3979 and 4377 IU/mL, respectively. These engineered strains showed more stable intracellular pH value during the fermentation process. Improvement of lactate production could partly provide the extra energy for the expression of acid tolerance genes during growth. Co-overexpression of hdeAB, murG, and ldh(Z) in strain F44 resulted in the nisin titer of 4913 IU/mL. The engineered strain (ABGL) could grow on plates with pH 4.2, comparing to the surviving pH 4.6 of strain F44. The fed-batch fermentation showed nisin titer of the co-expression L. lactis strain could reach 5563 IU/mL with lower pH condition and longer cultivation time. This work provides a novel strategy of constructing robust strains for use in industry process.

Co-overexpressing a Plasma Membrane and a Vacuolar Membrane Sodium/Proton Antiporter Significantly Improves Salt Tolerance in Transgenic Arabidopsis Plants.

PubMed

Pehlivan, Necla; Sun, Li; Jarrett, Philip; Yang, Xiaojie; Mishra, Neelam; Chen, Lin; Kadioglu, Asim; Shen, Guoxin; Zhang, Hong

2016-05-01

The Arabidopsis gene AtNHX1 encodes a vacuolar membrane-bound sodium/proton (Na(+)/H(+)) antiporter that transports Na(+) into the vacuole and exports H(+) into the cytoplasm. The Arabidopsis gene SOS1 encodes a plasma membrane-bound Na(+)/H(+) antiporter that exports Na(+) to the extracellular space and imports H(+) into the plant cell. Plants rely on these enzymes either to keep Na(+) out of the cell or to sequester Na(+) into vacuoles to avoid the toxic level of Na(+) in the cytoplasm. Overexpression of AtNHX1 or SOS1 could improve salt tolerance in transgenic plants, but the improved salt tolerance is limited. NaCl at concentration >200 mM would kill AtNHX1-overexpressing or SOS1-overexpressing plants. Here it is shown that co-overexpressing AtNHX1 and SOS1 could further improve salt tolerance in transgenic Arabidopsis plants, making transgenic Arabidopsis able to tolerate up to 250 mM NaCl treatment. Furthermore, co-overexpression of AtNHX1 and SOS1 could significantly reduce yield loss caused by the combined stresses of heat and salt, confirming the hypothesis that stacked overexpression of two genes could substantially improve tolerance against multiple stresses. This research serves as a proof of concept for improving salt tolerance in other plants including crops. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists.

Hydrodynamically Lubricated Rotary Shaft Having Twist Resistant Geometry

DOEpatents

Dietle, Lannie; Gobeli, Jeffrey D.

1993-07-27

A hydrodynamically lubricated squeeze packing type rotary shaft with a cross-sectional geometry suitable for pressurized lubricant retention is provided which, in the preferred embodiment, incorporates a protuberant static sealing interface that, compared to prior art, dramatically improves the exclusionary action of the dynamic sealing interface in low pressure and unpressurized applications by achieving symmetrical deformation of the seal at the static and dynamic sealing interfaces. In abrasive environments, the improved exclusionary action results in a dramatic reduction of seal and shaft wear, compared to prior art, and provides a significant increase in seal life. The invention also increases seal life by making higher levels of initial compression possible, compared to prior art, without compromising hydrodynamic lubrication; this added compression makes the seal more tolerant of compression set, abrasive wear, mechanical misalignment, dynamic runout, and manufacturing tolerances, and also makes hydrodynamic seals with smaller cross-sections more practical. In alternate embodiments, the benefits enumerated above are achieved by cooperative configurations of the seal and the gland which achieve symmetrical deformation of the seal at the static and dynamic sealing interfaces. The seal may also be configured such that predetermined radial compression deforms it to a desired operative configuration, even through symmetrical deformation is lacking.

Thermal tolerances of fishes occupying groundwater and surface-water dominated streams

USGS Publications Warehouse

Farless, Nicole; Brewer, Shannon K.

2017-01-01

A thermal tolerance study mimicking different stream environments could improve our ecological understanding of how increasing water temperatures affect stream ectotherms and improve our ability to predict organism responses based on river classification schemes. Our objective was to compare the thermal tolerances of stream fishes of different habitat guilds among 3 exposure periods: critical thermal maximum (CTmax, increase of 2°C/h until loss of equilibrium [LOE] and death [D]), and 2 longer-term treatments (net daily increase of 1°C) that mimicked spring-fed (SF; 4°C daily increase) and non-spring-fed (NSF; 8°C daily increase) conditions. Fishes in the pelagic habitat guild had a 1°C higher average CTmax than benthic fishes. Thermal responses of species depended on exposure period with higher and increased variation in tolerances associated with the SF and NSF exposure periods. Logperch, Orangebelly Darter, Orangethroat Darter, and Southern Redbelly Dace were more sensitive to thermal increases regardless of SF or NSF treatment than were the 3 remaining species (Brook Silverside, Central Stoneroller, and Redspot Chub), which represented average thermal responses among the species tested. The 3 species that had a higher thermal response to CTmax-D (lethal endpoint of death) also were able to increase their tolerances more than other species in both SF and NSF treatments. Our data indicate finer guild designations may be useful for predicting thermal-response patterns. A diel thermal refuge increases the thermal responses of ectotherms to daily maxima, but the patterns across our SF and NSF treatments were similar suggesting minimum refuge temperatures may be more important than maximums. Nonetheless, stream temperature cooling over a 24-h period is important to ectotherm thermal tolerances, a result suggesting that sources of cooler water to streams might benefit from protection.

Dietary chromium tripicolinate supplementation reduces glucose concentrations and improves glucose tolerance in normal-weight cats.

PubMed

Appleton, D J; Rand, J S; Sunvold, G D; Priest, J

2002-03-01

The effect of dietary chromium supplementation on glucose and insulin metabolism in healthy, non-obese cats was evaluated. Thirty-two cats were randomly divided into four groups and fed experimental diets consisting of a standard diet with 0 ppb (control), 150 ppb, 300 ppb, or 600 ppb added chromium as chromium tripicolinate. Intravenous glucose tolerance, insulin tolerance and insulin sensitivity tests with minimal model analysis were performed before and after 6 weeks of feeding the test diets. During the glucose tolerance test, glucose concentrations, area under the glucose concentration-time curve, and glucose half-life (300 ppb only), were significantly lower after the trial in cats supplemented with 300 ppb and 600 ppb chromium, compared with values before the trial. Fasting glucose concentrations measured on a different day in the biochemistry profile were also significantly lower after supplementation with 600 ppb chromium. There were no significant differences in insulin concentrations or indices in either the glucose or insulin tolerance tests following chromium supplementation, nor were there any differences between groups before or after the dietary trial.Importantly, this study has shown a small but significant, dose-dependent improvement in glucose tolerance in healthy, non-obese cats supplemented with dietary chromium. Further long-term studies are warranted to determine if the addition of chromium to feline diets is advantageous. Cats most likely to benefit are those with glucose intolerance and insulin resistance from lack of exercise, obesity and old age. Healthy cats at risk of glucose intolerance and diabetes from underlying low insulin sensitivity or genetic factors may also benefit from long-term chromium supplementation. Copyright 2002 ESFM and AAFP.

CSP41b, a protein identified via FOX hunting using Eutrema salsugineum cDNAs, improves heat and salinity stress tolerance in transgenic Arabidopsis thaliana.

PubMed

Ariga, Hirotaka; Tanaka, Tomoko; Ono, Hirokazu; Sakata, Yoichi; Hayashi, Takahisa; Taji, Teruaki

2015-08-14

Eutrema salsugineum (also known as Thellungiella salsuginea and formerly Thellungiella halophila), a species closely related to Arabidopsis thaliana, shows tolerance not only to salt stress, but also to chilling, freezing, and high temperatures. To identify genes responsible for stress tolerance, we conducted Full-length cDNA Over-eXpressing gene (FOX) hunting among a collection of E. salsugineum cDNAs that were stress-induced according to gene ontology analysis or over-expressed in E. salsugineum compared with A. thaliana. We identified E. salsugineum CSP41b (chloroplast stem-loop-binding protein of 41 kDa; also known as CRB, chloroplast RNA binding; named here as EsCSP41b) as a gene that can confer heat and salinity stress tolerance on A. thaliana. A. thaliana CSP41b is reported to play an important role in the proper functioning of the chloroplast: the atcsp41b mutant is smaller and paler than wild-type plants and shows altered chloroplast morphology and photosynthetic performance. We observed that AtCSP41b-overexpressing transgenic A. thaliana lines also exhibited marked heat tolerance and significant salinity stress tolerance. The EsCSP41b-overexpressing transgenic A. thaliana lines showed significantly higher photosynthesis activity than wild-type plants not only under normal growth conditions but also under heat stress. In wild-type plants, the expression levels of both EsCSP41b and AtCSP41b were significantly reduced under heat or salinity stress. We conclude that maintenance of CSP41b expression under abiotic stresses may alleviate photoinhibition and improve survival under such stresses. Copyright © 2015 Elsevier Inc. All rights reserved.

Improved tolerance to post-anthesis drought stress by pre-drought priming at vegetative stages in drought-tolerant and -sensitive wheat cultivars.

PubMed

Abid, Muhammad; Tian, Zhongwei; Ata-Ul-Karim, Syed Tahir; Liu, Yang; Cui, Yakun; Zahoor, Rizwan; Jiang, Dong; Dai, Tingbo

2016-09-01

Wheat crop endures a considerable penalty of yield reduction to escape the drought events during post-anthesis period. Drought priming under a pre-drought stress can enhance the crop potential to tolerate the subsequent drought stress by triggering a faster and stronger defense mechanism. Towards these understandings, a set of controlled moderate drought stress at 55-60% field capacity (FC) was developed to prime the plants of two wheat cultivars namely Luhan-7 (drought tolerant) and Yangmai-16 (drought sensitive) during tillering (Feekes 2 stage) and jointing (Feekes 6 stage), respectively. The comparative response of primed and non-primed plants, cultivars and priming stages was evaluated by applying a subsequent severe drought stress at 7 days after anthesis. The results showed that primed plants of both cultivars showed higher potential to tolerate the post-anthesis drought stress through improved leaf water potential, more chlorophyll, and ribulose-1, 5-bisphosphate carboxylase/oxygenase contents, enhanced photosynthesis, better photoprotection and efficient enzymatic antioxidant system leading to less yield reductions. The primed plants of Luhan-7 showed higher capability to adapt the drought stress events than Yangmai-16. The positive effects of drought priming to sustain higher grain yield were pronounced in plants primed at tillering than those primed at jointing. In consequence, upregulated functioning of photosynthetic apparatus and efficient enzymatic antioxidant activities in primed plants indicated their superior potential to alleviate a subsequently occurring drought stress, which contributed to lower yield reductions than non-primed plants. However, genotypic and priming stages differences in response to drought stress also contributed to affect the capability of primed plants to tolerate the post-anthesis drought stress conditions in wheat. Copyright © 2016. Published by Elsevier Masson SAS.

Mind-Body Skills Training to Improve Distress Tolerance in Medical Students: A Pilot Study.

PubMed

Kraemer, Kristen M; Luberto, Christina M; O'Bryan, Emily M; Mysinger, Erica; Cotton, Sian

2016-01-01

Medical students face rigorous and stressful work environments, resulting in high rates of psychological distress. However, there has been a dearth of empirical work aimed at modifying risk factors for psychopathology among this at-risk group. Distress tolerance, defined as the ability to withstand emotional distress, is one factor that may be important in promoting psychological well-being in medical students. Thus, the aim of the current mixed-methods study was (a) to describe changes in facets of distress tolerance (i.e., emotional tolerance, absorption, appraisal, regulation) for medical students who completed a mind-body skills training group, and a no-intervention control group of students; (b) to examine the relationship between changes in psychological variables and changes in distress tolerance; and (c) to report students' perceptions of the mind-body group, with an emphasis on how the group may have affected personal and professional functioning due to improvements in distress tolerance. The mind-body program was an 11-week, 2-hour skills training group that focused on introducing, practicing, and processing mind-body skills such as biofeedback, guided imagery, relaxation, several forms of meditation (e.g., mindfulness), breathing exercises, and autogenic training. Participants were 52 first- and second-year medical students (62.7% female, Mage = 23.45, SD = 1.51) who participated in a mind-body group or a no-intervention control group and completed self-report measures before and after the 11-week period. Students in the mind-body group showed a modest improvement in all distress tolerance subscales over time (ΔM = .42-.53, p = .01-.03, d = .44-.53), whereas the control group showed less consistent changes across most subscales (ΔM = .11-.42, p = .10-.65, d = .01-.42). Students in the mind-body group qualitatively reported an improved ability to tolerate affective distress. Overall, improvements in psychological symptoms were associated with improvements in distress tolerance in the mind-body group but not in the control group. These preliminary findings provide support for the notion that improving distress tolerance through mind-body skills training might serve to protect medical students from becoming functionally impaired by psychological distress. Thus, implementing mind-body skills training into medical school education may help to improve the psychological well-being of medical students. Future studies utilizing more methodologically rigorous designs are warranted.

A long-term, phase 2, multicenter, randomized, open-label, comparative safety study of pomaglumetad methionil (LY2140023 monohydrate) versus atypical antipsychotic standard of care in patients with schizophrenia

PubMed Central

2013-01-01

Background We compared the time to discontinuation due to lack of tolerability over 24 weeks in patients suffering from schizophrenia treated with pomaglumetad methionil (LY2140023 monohydrate, the prodrug of metabotropic glutamate 2/3 receptor agonist, LY404039) or standard of care (SOC: olanzapine, risperidone, or aripiprazole). Methods Study HBBR was a multicenter, randomized, open-label study comparing the long-term safety and tolerability of LY2140023 with SOC for schizophrenia. Patients had moderate symptomatology with prominent negative symptoms and evidence of functional impairment. Those who met entry criteria were randomized to open-label treatment with either LY2140023 (target dose: 40 mg twice daily [BID]; n = 130) or SOC (n = 131). Results There was no statistically significant difference between LY2140023 and SOC for time to discontinuation due to lack of tolerability (primary objective; P = .184). The Kaplan-Meier estimates revealed comparable time to event profiles. Only 27% of LY2140023 and 45% of SOC patients completed the 24-week open-label, active treatment phase. Twenty-seven patients (20.8%) in the LY2140023 group and 15 patients (11.5%) in the SOC group discontinued due to lack of efficacy (P = .044). Twenty-three patients (17.7%) in the LY2140023 group and 19 patients (14.5%) in the SOC group discontinued due to adverse events (physician and subject decision combined, P = .505). The incidence of serious adverse events was comparable between groups. LY2140023-treated patients reported significantly more treatment-emergent adverse events of vomiting, agitation, and dyspepsia, while SOC-treated patients reported significantly more akathisia and weight gain. The incidence of treatment-emergent parkinsonism (P = .011) and akathisia (P = .029) was significantly greater in SOC group. Improvement in PANSS total score over the initial 6 to 8 weeks of treatment was similar between groups, but improvement was significantly greater in the SOC group at 24-week endpoint (P = .004). LY2140023 and SOC groups had comparable negative symptom improvement at 24-week endpoint (P = .444). Conclusion These data provide further evidence that the potential antipsychotic LY2140023 monohydrate, with a glutamatergic mechanism of action, may have a unique tolerability profile characterized by a low association with some adverse events such as extrapyramidal symptoms and weight gain that may characterize currently available dopaminergic antipsychotics. Trials registration A Long-term, Phase 2, Multicenter, Randomized, Open-label, Comparative Safety Study of LY2140023 Versus Atypical Antipsychotic Standard of Care in Patients with DSM-IV-TR Schizophrenia ClinicalTrials.gov identifier: NCT00845026. PMID:23694720

Lipophilic components of the brown seaweed, Ascophyllum nodosum, enhance freezing tolerance in Arabidopsis thaliana.

PubMed

Rayirath, Prasanth; Benkel, Bernhard; Mark Hodges, D; Allan-Wojtas, Paula; Mackinnon, Shawna; Critchley, Alan T; Prithiviraj, Balakrishnan

2009-06-01

Extracts of the brown seaweed Ascophyllum nodosum enhance plant tolerance against environmental stresses such as drought, salinity, and frost. However, the molecular mechanisms underlying this improved stress tolerance and the nature of the bioactive compounds present in the seaweed extracts that elicits stress tolerance remain largely unknown. We investigated the effect of A. nodosum extracts and its organic sub-fractions on freezing tolerance of Arabidopsis thaliana. Ascophyllum nodosum extracts and its lipophilic fraction significantly increased tolerance to freezing temperatures in in vitro and in vivo assays. Untreated plants exhibited severe chlorosis, tissue damage, and failed to recover from freezing treatments while the extract-treated plants recovered from freezing temperature of -7.5 degrees C in in vitro and -5.5 degrees C in in vivo assays. Electrolyte leakage measurements revealed that the LT(50) value was lowered by 3 degrees C while cell viability staining demonstrated a 30-40% reduction in area of damaged tissue in extract treated plants as compared to water controls. Moreover, histological observations of leaf sections revealed that extracts have a significant effect on maintaining membrane integrity during freezing stress. Treated plants exhibited 70% less chlorophyll damage during freezing recovery as compared to the controls, and this correlated with reduced expression of the chlorphyllase genes AtCHL1 and AtCHL2. Further, the A. nodosum extract treatment modulated the expression of the cold response genes, COR15A, RD29A, and CBF3, resulting in enhanced tolerance to freezing temperatures. More than 2.6-fold increase in expression of RD29A, 1.8-fold increase of CBF3 and two-fold increase in the transcript level of COR15A was observed in plants treated with lipophilic fraction of A. nodosum at -2 degrees C. Taken together, the results suggest that chemical components in A. nodosum extracts protect membrane integrity and affect the expression of stress response genes leading to freezing stress tolerance in A. thaliana.

Can we well assess the relative efficacy and tolerability of a new drug versus others at the time of marketing authorization using mixed treatment comparisons? A detailed illustration with escitalopram.

PubMed

Llorca, Pierre-Michel; Lançon, Christophe; Brignone, Mélanie; Painchault, Caroline; Rive, Benoit; Toumi, Mondher; François, Clément

2015-01-01

To assess the variation of relative efficacy and tolerability of an antidepressant versus others based on both pre-marketing (registration studies) and post-marketing studies versus pre-marketing studies only in patients with major depressive disorder. The relative efficacy and tolerability of antidepressants was assessed by mixed treatment comparisons (MTCs) using data acquired over two time periods: before registration of the reference drug escitalopram (1989-2002) and up to 5 years later (1989-2007). Ranking probability outputs were presented for efficacy, using change from baseline to 8 weeks on Montgomery-Åsberg Depression Rating Scale total score, and tolerability, using withdrawals due to adverse events. The relative efficacy and tolerability of some selected antidepressants, including escitalopram, varied considerably over the two time periods. The improved relative efficacy and tolerability of escitalopram over time, compared with citalopram, was demonstrated by greater separation of ranking probability curves for efficacy and tolerability. In 2002, escitalopram ranked low with 13.9% and 5.1% probability of being in the top four antidepressants' relative efficacy and tolerability, respectively. In 2007, ranking probabilities for relative efficacy and tolerability of escitalopram increased to 52.5% and 82.1%, respectively. Time of marketing authorization may not be the most appropriate time to evaluate the relative efficacy and tolerability of a new antidepressant based on MTC approach due to the asymmetry of information between new and older compounds. However, the first evaluation of relative effect of a new drug for health technology assessment recommendations is commonly done at this time. Re-evaluation of a drug several years after its launch is likely to provide a more accurate indication of its relative efficacy and tolerability.

Realm of Thermoalkaline Lipases in Bioprocess Commodities.

PubMed

Lajis, Ahmad Firdaus B

2018-01-01

For decades, microbial lipases are notably used as biocatalysts and efficiently catalyze various processes in many important industries. Biocatalysts are less corrosive to industrial equipment and due to their substrate specificity and regioselectivity they produced less harmful waste which promotes environmental sustainability. At present, thermostable and alkaline tolerant lipases have gained enormous interest as biocatalyst due to their stability and robustness under high temperature and alkaline environment operation. Several characteristics of the thermostable and alkaline tolerant lipases are discussed. Their molecular weight and resistance towards a range of temperature, pH, metal, and surfactants are compared. Their industrial applications in biodiesel, biodetergents, biodegreasing, and other types of bioconversions are also described. This review also discusses the advance of fermentation process for thermostable and alkaline tolerant lipases production focusing on the process development in microorganism selection and strain improvement, culture medium optimization via several optimization techniques (i.e., one-factor-at-a-time, surface response methodology, and artificial neural network), and other fermentation parameters (i.e., inoculums size, temperature, pH, agitation rate, dissolved oxygen tension (DOT), and aeration rate). Two common fermentation techniques for thermostable and alkaline tolerant lipases production which are solid-state and submerged fermentation methods are compared and discussed. Recent optimization approaches using evolutionary algorithms (i.e., Genetic Algorithm, Differential Evolution, and Particle Swarm Optimization) are also highlighted in this article.

Three cycles of water deficit from seed to young plants of Moringa oleifera woody species improves stress tolerance.

PubMed

Rivas, Rebeca; Oliveira, Marciel T; Santos, Mauro G

2013-02-01

The main objective of this study was to assess whether recurring water stress occurring from seed germination to young plants of Moringa oleifera Lam. are able to mitigate the drought stress effects. Germination, gas exchange and biochemical parameters were analysed after three cycles of water deficit. Young plants were used 50 days after germination under three osmotic potentials (0.0, -0.3 and -0.4 MPa). For each germination treatment, control (irrigated) and stressed (10% of water control) plants were compared for a total of six treatments. There were two cycles of drought interspersed with 10 days of rehydration. The young plants of M. oleifera showed increased tolerance to repeated cycles of drought, maintaining high relative water content (RWC), high water use efficiency (WUE), increased photosynthetic pigments and increased activity of antioxidant enzymes. There was rapid recovery of the photosynthetic rate during the rehydration period. The stressed plants from the -0.3 and -0.4 MPa treatments showed higher tolerance compared to the control plants. The results suggest that seeds of M. oleifera subjected to mild water deficit have had increased the ability for drought tolerance when young plant. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Efficacy of the addition of salicylic acid to clindamycin and benzoyl peroxide combination for acne vulgaris.

PubMed

Akarsu, Sevgi; Fetil, Emel; Yücel, Filiz; Gül, Eylem; Güneş, Ali T

2012-05-01

Clindamycin phosphate (CDP), benzoyl peroxide (BPO) and salicylic acid (SA) are known to be effective acne therapy agents depending on their anti-inflammatory and comedolytic properties. The purpose of this study was to investigate the efficacy and tolerability of the addition of SA treatment to CDP and BPO (SA and CDP + BPO) and compare it with CDP + BPO in patients with mild to moderate facial acne vulgaris. Forty-nine patients were enrolled in a 12 week prospective, single-blind, randomized, comparative clinical study. Efficacy was assessed by lesion counts, global improvement, quality of life index and measurements of skin barrier functions. Local side effects were also evaluated. Both combinations were effective in reducing total lesion (TL), inflammatory lesion (IL) and non-inflammatory lesion (NIL) counts. There were statistically significant differences between treatment groups for reductions in NIL counts beyond 2 weeks, IL counts and TL counts throughout the all study weeks, and global improvement scores evaluated by patients and investigator at the end of the study in favor of SA and CDP + BPO treatment when compared to CDP + BPO treatment. Both combinations significantly decreased stratum corneum hydration, although skin sebum values decreased with SA and CDP + BPO treatment. These combinations were also well tolerated except significantly higher frequency of mild to moderate transient dryness in patients applied SA and CDP + BPO. The addition of SA to CDP + BPO treatment demonstrated significantly better and faster results in terms of reductions in acne lesion counts and well tolerated except for higher frequency of mild to moderate transient dryness. © 2011 Japanese Dermatological Association.

The influences of Cr-tolerant rhizobacteria in phytoremediation and attenuation of Cr (VI) stress in agronomic sunflower (Helianthus annuus L.).

PubMed

Bahadur, Ali; Ahmad, Rizwan; Afzal, Aftab; Feng, Huyuan; Suthar, Vishandas; Batool, Asfa; Khan, Aman; Mahmood-Ul-Hassan, Muhammad

2017-07-01

Chromium contamination of agronomic soil has to turn into a serious global problem. This research was pointed to assess the effects of three Cr-tolerant rhizobacteria (SS1, SS3, and SS6) on sunflower growth and heavy metal uptake under Cr smog i.e. 20, 30 and 40 ppm using K 2 Cr 2 O 7 . Root promotion assay and pot experiment were conducted to investigate and evaluate the effects of Cr tolerance rhizobacteria and Cr accumulation capacity of sunflower. From root promotion assay non-significant variation was observed in the root length between SS1 and SS3 compared with un-inoculated whereas SS6 enhanced the root length in the absence and presence of chromium. In addition, inoculation with rhizobacteria alleviated the Cr concentration and endorsed plant growth by enhancing Cr accumulation in sunflower. At different Cr levels, the Cr concentration in shoot was improved by each rhizobacterium though their difference was non-significant with each other, while the percentage increase was half as the Cr level doubled. Different rhizobacterium inoculation significantly (P < 0.05) affected the physiological and morphological characteristics of sunflower and increased the plant height, stem diameter, head diameter, grain yield, oil content of seeds, and total biomass, and among them, SS6 observed best followed by SS1 and SS3 comparing with un-inoculated. Our study illustrates an assessment about Cr-tolerant bacteria and their influences and recommends that these bacteria can effectively be used for crop improvement which provides a potential approach for Cr phytoremediation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Tesaglitazar, a dual PPAR{alpha}/{gamma} agonist, ameliorates glucose and lipid intolerance in obese Zucker rats.

PubMed

Oakes, Nicholas D; Thalén, Pia; Hultstrand, Therese; Jacinto, Severina; Camejo, Germán; Wallin, Boel; Ljung, Bengt

2005-10-01

Insulin resistance, impaired glucose tolerance, high circulating levels of free fatty acids (FFA), and postprandial hyperlipidemia are associated with the metabolic syndrome, which has been linked to increased risk of cardiovascular disease. We studied the metabolic responses to an oral glucose/triglyceride (TG) (1.7/2.0 g/kg lean body mass) load in three groups of conscious 7-h fasted Zucker rats: lean healthy controls, obese insulin-resistant/dyslipidemic controls, and obese rats treated with the dual peroxisome proliferator-activated receptor alpha/gamma agonist, tesaglitazar, 3 mumol.kg(-1).day(-1) for 4 wk. Untreated obese Zucker rats displayed marked insulin resistance, as well as glucose and lipid intolerance in response to the glucose/TG load. The 2-h postload area under the curve values were greater for glucose (+19%), insulin (+849%), FFA (+53%), and TG (+413%) compared with untreated lean controls. Treatment with tesaglitazar lowered fasting plasma glucose, improved glucose tolerance, substantially reduced fasting and postload insulin levels, and markedly lowered fasting TG and improved lipid tolerance. Fasting FFA were not affected, but postprandial FFA suppression was restored to levels seen in lean controls. Mechanisms of tesaglitazar-induced lowering of plasma TG were studied separately using the Triton WR1339 method. In anesthetized, 5-h fasted, obese Zucker rats, tesaglitazar reduced hepatic TG secretion by 47%, increased plasma TG clearance by 490%, and reduced very low-density lipoprotein (VLDL) apolipoprotein CIII content by 86%, compared with obese controls. In conclusion, the glucose/lipid tolerance test in obese Zucker rats appears to be a useful model of the metabolic syndrome that can be used to evaluate therapeutic effects on impaired postprandial glucose and lipid metabolism. The present work demonstrates that tesaglitazar ameliorates these abnormalities and enhances insulin sensitivity in this animal model.

Fasting hyperglycaemia blunts the reversal of impaired glucose tolerance after exercise training in obese older adults.

PubMed

Malin, S K; Kirwan, J P

2012-09-01

Lifestyle modification, consisting of exercise and weight loss, delays the progression from prediabetes to type 2 diabetes (T2D). However, no study has determined the efficacy of exercise training on glucose metabolism in the different prediabetes subtypes. Seventy-six older (65.1 ± 0.6 years) obese adults with impaired fasting glucose (IFG; n = 12), impaired glucose tolerance (IGT; n = 9) and combined glucose intolerance (IFG + IGT = CGI; n = 22) were compared with normal glucose tolerant (NGT; n = 15) and T2D (n = 18) groups after 12 weeks of exercise training (60 min/day for 5 days/week at ~85% HR(max)). An oral glucose tolerance test was used to assess glucose levels. Insulin sensitivity (IS; euglycaemic hyperinsulinaemic clamp at 40 mU/m(2)/min), β-cell function (glucose-stimulated insulin secretion corrected for IS), body composition (hydrostatic weighing/computed tomography scan) and cardiovascular fitness (treadmill VO(2) max) were also assessed. Exercise training reduced weight and increased cardiovascular fitness (p < 0.05). Exercise training lowered fasting glucose levels in IFG, CGI and T2D (p < 0.05) and 2-h glucose levels in IGT, CGI and T2D (p < 0.05). However, 2-h glucose levels were not normalized in adults with CGI compared with IGT (p < 0.05). β-Cell function improved similarly across groups (p < 0.05). Although not statistically significant, IS increased approximately 40% in IFG and IGT, but only 17% in CGI. The magnitude of improvement in glucose metabolism after 12 weeks of exercise training is not uniform across the prediabetes subtypes. Given the high risk of progressing to T2D, adults with CGI may require more aggressive therapies to prevent diabetes. © 2012 Blackwell Publishing Ltd.

Efficacy and tolerability of paracetamol/tramadol (325 mg/37.5 mg) combination treatment compared with tramadol (50 mg) monotherapy in patients with subacute low back pain: a multicenter, randomized, double-blind, parallel-group, 10-day treatment study.

PubMed

Perrot, Serge; Krause, Dirk; Crozes, Philippe; Naïm, Claude

2006-10-01

In various pain studies, the single-dose combination of paracetamol/tramadol (PIT) was found to be more effective than either agent alone. PIT could provide benefit in patients with subacute low back pain (LBP). This study compared the efficacy and tolerability of PIT with tramadol alone (T) in patients with subacute LBP and assessed whether, under comparable analgesic conditions, PIT would be better tolerated. This was a multicenter, randomized, double-blind, parallel-group study. Patients were enrolled if they suffered from nonspecific LBP lasting 10 to 42 days and experienced at least moderate pain (> or =40 mm on a 100-mm visual analog scale). Patients were randomized and treated for 10 days with PIT (325 mg/37.5 mg) or T (50 mg). The study outcomes were treatment efficacy (pain intensity, pain relief, patient satisfaction, physicians' assessment of pain control) and tolerability (adverse events [AEs], patients' tolerability judgment). A total of 119 patients were enrolled (PIT, n = 59; T, n = 60). Demographic characteristics of patients were comparable between the PIT and T groups in regard to age (mean, 56.5 vs 54.1 years, respectively), sex (women/men, 38121 vs 31129), race (white, 96.1% vs 94.2%), and body mass index (24.9 vs 26.1 kg/m2). Pain intensity (mean [SD] percentage of worst imaginable pain) improved from nearly identical levels at baseline (P/T, 67.5 [13.0] vs T, 65.3 [14.6]; P = NS) to similarly low levels at the final visit (P/T, 27.9 [22.7] vs T, 24.8 [21.6]; P = NS). The reduction in pain intensity was significant in both treatment groups (P < 0.001). Adequate pain relief (ie, "moderate," "important," or "complete") was observed in 81.6% (40149) of PIT patients versus 82.9% (39147) of T patients (P = NS). Comparably high rates of overall patient satisfaction (72.5% [37151] vs 72.9% [35148], respectively; P = NS) were achieved. Both treatment groups took a comparable number of daily units of study medication, which resulted in significantly (P < 0.001) lower daily doses of tramadol in the P/T group (mean [SD], 172.5 [46.6] mg) than in the T group (227.3 [59.7] mg). More P/T patients (84.3%) than T patients (68.8%) judged treatment tolerability as good or very good (P = NS). Significantly fewer AEs (P < 0.001) were observed in PIT patients, and the overall incidence of AEs (mostly opioid-typical AEs [eg, nausea, dizziness/vertigo, sleepiness/drowsiness, constipation, vomiting]) was much lower after P/T compared with T (P = 0.019). The most common AEs in the P/T and T groups were nausea (8159 vs 21160 patients, respectively; P = 0.012) and dizziness (3/59 vs 15/60 patients; P= 0.006). Tramadol, alone and in combination with paracetamol, provided highly effective analgesia for these patients with subacute LSP However, the combination of PIT, which resulted in 25% less tramadol than equianalgesic daily doses of T alone, considerably reduced the incidence of AEs and improved tolerability.

Comparative Efficacy of Newer Antidepressants in Combination with Pregabalin for Fibromyalgia Syndrome: A Controlled, Randomized Study.

PubMed

Ramzy, Eiad A

2017-01-01

This controlled, randomized study investigated the hypothesis that the combined use of pregabalin plus paroxetine for fibromyalgia management would be associated with comparable Somatic Symptoms Scale-8 (SSS-8) and Center for Epidemiological Studies Depression Scale (CESDS) scores, but higher tolerability than the combined use of pregabalin plus either amitriptyline or venlafaxine. After institutional ethics committee approval, 75 female subjects diagnosed with fibromyalgia and in receipt of pregabalin (75 mg/day) were randomly allocated to concurrently receive amitriptyline (25 mg/day; n = 24), venlafaxine (75 mg/day; n = 25), or paroxetine (25 mg/day; n = 26). All patients were assessed bimonthly for 6 consecutive months for changes in SSS-8 and CESDS scores, life satisfaction, mood, sleep quality, fatigue, medication tolerability, and adverse events. Compared with pregabalin plus amitriptyline or venlafaxine, the combined use of pregabalin plus paroxetine in fibromyalgia patients resulted in significantly lower SSS-8 and CESDS scores from 18 (P < 0.05) and 10 weeks (P < 0.001) after the initiation of study medications, respectively; higher medication tolerability (P < 0.001); improved life satisfaction, mood, and sleep quality at most observation times (P < 0.05); and fewer instances of dry mouth and elevated blood pressure (P < 0.02). Medication termination due to poor tolerability was observed most frequently in the venlafaxine group (P < 0.05), while drowsiness, dizziness, blurred vision, abnormal taste, hunger, hallucination, urination problems, and sexual dysfunction were observed most frequently in the amitriptyline group (P < 0.02). The combined use of pregabalin plus paroxetine offers an effective method with increased tolerability to reduce the somatic and depressive symptoms of fibromyalgia and to enhance the quality of life in affected individuals. © 2016 World Institute of Pain.

The Potential of Transcription Factor-Based Genetic Engineering in Improving Crop Tolerance to Drought

PubMed Central

Tripathi, Prateek

2014-01-01

Abstract Drought is one of the major constraints in crop production and has an effect on a global scale. In order to improve crop production, it is necessary to understand how plants respond to stress. A good understanding of regulatory mechanisms involved in plant responses during drought will enable researchers to explore and manipulate key regulatory points in order to enhance stress tolerance in crops. Transcription factors (TFs) have played an important role in crop improvement from the dawn of agriculture. TFs are therefore good candidates for genetic engineering to improve crop tolerance to drought because of their role as master regulators of clusters of genes. Many families of TFs, such as CCAAT, homeodomain, bHLH, NAC, AP2/ERF, bZIP, and WRKY have members that may have the potential to be tools for improving crop tolerance to drought. In this review, the roles of TFs as tools to improve drought tolerance in crops are discussed. The review also focuses on current strategies in the use of TFs, with emphasis on several major TF families in improving drought tolerance of major crops. Finally, many promising transgenic lines that may have improved drought responses have been poorly characterized and consequently their usefulness in the field is uncertain. New advances in high-throughput phenotyping, both greenhouse and field based, should facilitate improved phenomics of transgenic lines. Systems biology approaches should then define the underlying changes that result in higher yields under water stress conditions. These new technologies should help show whether manipulating TFs can have effects on yield under field conditions. PMID:25118806

Short-term and long-term effects of guar on postprandial plasma glucose, insulin and glucagon-like peptide 1 concentration in healthy rats.

PubMed

Prieto, P G; Cancelas, J; Villanueva-Peñacarrillo, M L; Malaisse, W J; Valverde, I

2006-06-01

Ingestion of guar gum decreases postprandial glycemia and insulinemia and improves sensitivity to insulin in diabetic patients and several animal models of diabetes. The aim of the present study was to compare the short-term and long-term effects of guar on plasma insulin and glucagon-like peptide 1 concentration in healthy rats. In the short-term experiments, the concomitant intragastric administration of glucose and guar reduced the early increment in plasma glucose, insulin and glucagon-like peptide 1 concentration otherwise induced by glucose alone. Comparable findings were made after twelve days of meal training exposing the rats to either a control or guar-enriched diet for fifteen minutes. Mean plasma glucose concentrations were lower while mean insulin concentrations were higher in the guar group than in the controls according to intragastric glucose tolerance tests conducted in overnight fasted rats maintained for 19 to 36 days on either the control or guar-enriched diet. The intestinal content of glucagon-like peptide 1 at the end of the experiments was also lower in the guar group. Changes in body weight over 62 days of observation were comparable in the control and guar rats. Thus, long-term intake of guar improves glucose tolerance and insulin response to glucose absorption, without improving insulin sensitivity, in healthy rats.

The regulatory T cell effector molecule fibrinogen-like protein 2 is necessary for the development of rapamycin-induced tolerance to fully MHC-mismatched murine cardiac allografts

PubMed Central

Urbanellis, Peter; Shyu, Wendy; Khattar, Ramzi; Wang, Jihong; Zakharova, Anna; He, Wei; Sadozai, Hassan; Amir, Achiya Z; Shalev, Itay; Phillips, M James; Adeyi, Oyedele; Ross, Heather; Grant, David; Levy, Gary A; Chruscinski, Andrzej

2015-01-01

Therapies that promote tolerance in solid organ transplantation will improve patient outcomes by eliminating the need for long-term immunosuppression. To investigate mechanisms of rapamycin-induced tolerance, C3H/HeJ mice were heterotopically transplanted with MHC-mismatched hearts from BALB/cJ mice and were monitored for rejection after a short course of rapamycin treatment. Mice that had received rapamycin developed tolerance with indefinite graft survival, whereas untreated mice all rejected their grafts within 9 days. In vitro, splenic mononuclear cells from tolerant mice maintained primary CD4+ and CD8+ immune responses to donor antigens consistent with a mechanism that involves active suppression of immune responses. Furthermore, infection with lymphocytic choriomeningitis virus strain WE led to loss of tolerance suggesting that tolerance could be overcome by infection. Rapamycin-induced, donor-specific tolerance was associated with an expansion of regulatory T (Treg) cells in both the spleen and allograft and elevated plasma levels of fibrinogen-like protein 2 (FGL2). Depletion of Treg cells with anti-CD25 (PC61) and treatment with anti-FGL2 antibody both prevented tolerance induction. Tolerant allografts were populated with Treg cells that co-expressed FGL2 and FoxP3, whereas rejecting allografts and syngeneic grafts were nearly devoid of dual-staining cells. We examined the utility of an immunoregulatory gene panel to discriminate between tolerance and rejection. We observed that Treg-associated genes (foxp3, lag3, tgf-β and fgl2) had increased expression and pro-inflammatory genes (ifn-γ and gzmb) had decreased expression in tolerant compared with rejecting allografts. Taken together, these data strongly suggest that Treg cells expressing FGL2 mediate rapamycin-induced tolerance. Furthermore, a gene biomarker panel that includes fgl2 can distinguish between rejecting and tolerant grafts. PMID:24990517

A single bout of high-intensity interval exercise and work-matched moderate-intensity exercise has minimal effect on glucose tolerance and insulin sensitivity in 7- to 10-year-old boys.

PubMed

Cockcroft, Emma J; Williams, Craig A; Jackman, Sarah R; Bassi, Shikhar; Armstrong, Neil; Barker, Alan R

2018-01-01

The purpose of this study was to assess the acute effect of high-intensity interval exercise (HIIE) and moderate-intensity exercise (MIE) on glucose tolerance, insulin sensitivity and fat oxidation in young boys. Eleven boys (8.8 ± 0.8 y) completed three conditions: 1) HIIE; 2) work-matched MIE; and 3) rest (CON) followed by an oral glucose tolerance test (OGTT) to determine glucose tolerance and insulin sensitivity (Cederholm index). Fat oxidation was measured following the OGTT using indirect calorimetry. There was no effect for condition on plasma [glucose] and [insulin] area under the curve (AUC) responses following the OGTT (P > 0.09). However, there was a "trend" for a condition effect for insulin sensitivity with a small increase after HIIE (P = 0.04, ES = 0.28, 9.7%) and MIE (P = 0.07, ES = 0.21, 6.5%) compared to CON. There was an increase in fat oxidation AUC following HIIE (P = 0.008, ES = 0.79, 38.9%) compared to CON, but with no differences between MIE and CON and HIIE and MIE (P > 0.13). In conclusion, 7- to 10-year-old boys may have limited scope to improve insulin sensitivity and glucose tolerance after a single bout of HIIE and MIE. However, fat oxidation is augmented after HIIE but not MIE.

Local tolerance and stability up to 24 months of a new 20% proline-stabilized polyclonal immunoglobulin for subcutaneous administration.

PubMed

Maeder, Werner; Lieby, Patricia; Sebald, Andrea; Spycher, Martin; Pedrussio, Renzo; Bolli, Reinhard

2011-01-01

Subcutaneous administration of human IgG is an alternative to intravenous replacement therapy that is associated with more stable serum IgG levels and fewer systemic adverse events. Highly concentrated IgG solutions are most convenient to minimize infusion volume, but their preparation and stability presents substantial technical difficulties. We report on the stability and local tolerance of IgPro20, an l-proline-stabilized, 20% polyvalent human IgG developed for subcutaneous administration. Stability was tested according to ICH guidelines. Local tolerance and vasoactivity were examined in rabbit and rat models, respectively. The presence of l-proline in IgPro20 reduced viscosity and addition of Polysorbate 80 and inert gassing improved the appearance of the solution. After storage at 25 °C for 24 months, monomer + dimer content, aggregates, and fragments were within specification (≥ 90.0%, ≤ 4.0%, and ≤ 10.0%, respectively), and Fc function and antibody activities were maintained. In rats, intravenous injection of IgPro20 produced mild and transient hypotension comparable to that seen with intravenous IgG products. Local tolerance of IgPro20 in rabbits was comparable to that of a marketed subcutaneous IgG, Beriglobin P. Functionality and quality of IgPro20 are maintained during storage at 25 °C for at least 24 months. The product is well tolerated as assessed in animal models. Copyright © 2010 The International Association for Biologicals. Published by Elsevier Ltd. All rights reserved.

Improving the acetic acid tolerance and fermentation of Acetobacter pasteurianus by nucleotide excision repair protein UvrA.

PubMed

Zheng, Yu; Wang, Jing; Bai, Xiaolei; Chang, Yangang; Mou, Jun; Song, Jia; Wang, Min

2018-05-21

Acetic acid bacteria (AAB) are widely used in acetic acid fermentation due to their remarkable ability to oxidize ethanol and high tolerance against acetic acid. In Acetobacter pasteurianus, nucleotide excision repair protein UvrA was up-regulated 2.1 times by acetic acid when compared with that without acetic acid. To study the effects of UvrA on A. pasteurianus acetic acid tolerance, uvrA knockout strain AC2005-ΔuvrA, uvrA overexpression strain AC2005 (pMV24-uvrA), and the control strain AC2005 (pMV24), were constructed. One percent initial acetic acid was almost lethal to AC2005-ΔuvrA. However, the biomass of the UvrA overexpression strain was higher than that of the control under acetic acid concentrations. After 6% acetic acid shock for 20 and 40 min, the survival ratios of AC2005 (pMV24-uvrA) were 2 and 0.12%, respectively; however, they were 1.5 and 0.06% for the control strain AC2005 (pMV24). UvrA overexpression enhanced the acetification rate by 21.7% when compared with the control. The enzymes involved in ethanol oxidation and acetic acid tolerance were up-regulated during acetic acid fermentation due to the overexpression of UvrA. Therefore, in A. pasteurianus, UvrA could be induced by acetic acid and is related with the acetic acid tolerance by protecting the genome against acetic acid to ensure the protein expression and metabolism.

Oxygation enhances growth, gas exchange and salt tolerance of vegetable soybean and cotton in a saline vertisol.

PubMed

Bhattarai, Surya P; Midmore, David J

2009-07-01

Impacts of salinity become severe when the soil is deficient in oxygen. Oxygation (using aerated water for subsurface drip irrigation of crop) could minimize the impact of salinity on plants under oxygen-limiting soil environments. Pot experiments were conducted to evaluate the effects of oxygation (12% air volume/volume of water) on vegetable soybean (moderately salt tolerant) and cotton (salt tolerant) in a salinized vertisol at 2, 8, 14, 20 dS/m EC(e). In vegetable soybean, oxygation increased above ground biomass yield and water use efficiency (WUE) by 13% and 22%, respectively, compared with the control. Higher yield with oxygation was accompanied by greater plant height and stem diameter and reduced specific leaf area and leaf Na+ and Cl- concentrations. In cotton, oxygation increased lint yield and WUE by 18% and 16%, respectively, compared with the control, and was accompanied by greater canopy light interception, plant height and stem diameter. Oxygation also led to a greater rate of photosynthesis, higher relative water content in the leaf, reduced crop water stress index and lower leaf water potential. It did not, however, affect leaf Na+ or Cl- concentration. Oxygation invariably increased, whereas salinity reduced the K+ : Na+ ratio in the leaves of both species. Oxygation improved yield and WUE performance of salt tolerant and moderately tolerant crops under saline soil environments, and this may have a significant impact for irrigated agriculture where saline soils pose constraints to crop production.

Phototrophic cultivation of NaCl-tolerant mutant of Spirulina platensis for enhanced C-phycocyanin production under optimized culture conditions and its dynamic modeling.

PubMed

Gupta, Apurva; Mohan, Devendra; Saxena, Rishi Kumar; Singh, Surendra

2018-02-01

Commercial cultivation of Spirulina sp. is highly popular due to the presence of high amount of C-phycocyanin (C-PC) and other valuable chemicals like carotenoids and γ-linolenic acid. In this study, the pH and the concentrations of nitrogen and carbon source were manipulated to achieve improved cell growth and C-PC production in NaCl-tolerant mutant of Spirulina platensis. In this study, highest C-PC (147 mg · L -1 ) and biomass (2.83 g · L -1 ) production was achieved when a NaCl-tolerant mutant of S. platensis was cultivated in a nitrate and bicarbonate sufficient medium (40 and 60 mM, respectively) at pH 9.0 under phototrophic conditions. Kinetic study of wildtype S. platensis and its NaCl-tolerant mutant was also done to determine optimum nitrate concentrations for maximum growth and C-PC production. Kinetic parameter of inhibition (Haldane model) was fitted to the relationship between specific growth rate and substrate concentration obtained from the growth curves. Results showed that the maximum specific growth rate (μ max ) for NaCl-tolerant mutant increased by 17.94% as compared to its wildtype counterpart, with a slight increase in half-saturation constant (K s ), indicating that this strain could grow well at high concentration of NaNO 3 . C-PC production rate (C max ) in mutant cells increased by 12.2% at almost half the value of K s as compared to its wildtype counterpart. Moreover, the inhibition constant (K i ) value was 207.85% higher in NaCl-tolerant mutant as compared to its wildtype strain, suggesting its ability to produce C-PC even at high concentrations of NaNO 3 . © 2017 Phycological Society of America.

Comparing Safety and Efficacy of "Third-Generation" Antiepileptic Drugs: Long-Term Extension and Post-marketing Treatment.

PubMed

Kwok, Charlotte S; Johnson, Emily L; Krauss, Gregory L

2017-11-01

Four "third-generation" antiepileptic drugs (AEDs) were approved for adjunctive treatment of refractory focal onset seizures during the past 10 years. Long-term efficacy and safety of the drugs were demonstrated in large extension studies and in reports of subgroups of patients not studied in pivotal trials. Reviewing extension study and post-marketing outcome series for the four newer AEDs-lacosamide, perampanel, eslicarbazepine acetate and brivaracetam-can guide clinicians in treating and monitoring patients. AED extension studies evaluate treatment retention, drug tolerability, and drug safety during individualized treatment with flexible dosing and thus provide information not available in rigid pivotal trials. Patient retention in the studies ranged from 75 to 80% at 1 year and from 36 to 68% at 2-year treatment intervals. Safety findings were generally similar to those of pivotal trials, with no major safety risks identified and with several specific adverse drug effects, such as hyponatremia, reported. The third-generation AEDs, some through new mechanisms and others with improved tolerability compared to related AEDs, provide new options in efficacy and tolerability.

[Efficacy and tolerability of cisapride in a new formula of 10 mg effervescent capsules for the treatment of functional dyspepsia].

PubMed

Grossi, L; Di Felice, F; Marzio, L

1993-06-01

The efficacy and tolerability of Cisapride effervescent granules and a metoclopramide-dimethicone combination were compared double-blind in two comparable groups of 15 patients each with dyspepsia. All patients received three sachets daily of either drug for 6 consecutive weeks. As for efficacy, Cisapride effervescent granules was found to reduce 85% (11/13) of symptoms to a statistically significant extent, as against 42% (5/12) in the reference group. Statistical analysis showed Cisapride effervescent granules to be more effective than the reference drug for 6 out of 11 evaluable symptoms. Mean global improvement was 86% for Cisapride effervescent granules vs 41% for the reference combination. Final judgment by the physician was more favorable for Cisapride effervescent granules than for the reference drug (p < 0.0001). Treatment withdrawal was never necessary and no significant changes of laboratory values were observed. No statistically significant difference between the two treatments as to tolerability was observed. In conclusion, Cisapride effervescent granules was found to have a better risk/benefit ratio than the reference combination.

Cold acclimation wholly reorganizes the Drosophila melanogaster transcriptome and metabolome

PubMed Central

MacMillan, Heath A.; Knee, Jose M.; Dennis, Alice B.; Udaka, Hiroko; Marshall, Katie E.; Merritt, Thomas J. S.; Sinclair, Brent J.

2016-01-01

Cold tolerance is a key determinant of insect distribution and abundance, and thermal acclimation can strongly influence organismal stress tolerance phenotypes, particularly in small ectotherms like Drosophila. However, there is limited understanding of the molecular and biochemical mechanisms that confer such impressive plasticity. Here, we use high-throughput mRNA sequencing (RNA-seq) and liquid chromatography – mass spectrometry (LC-MS) to compare the transcriptomes and metabolomes of D. melanogaster acclimated as adults to warm (rearing) (21.5 °C) or cold conditions (6 °C). Cold acclimation improved cold tolerance and led to extensive biological reorganization: almost one third of the transcriptome and nearly half of the metabolome were differentially regulated. There was overlap in the metabolic pathways identified via transcriptomics and metabolomics, with proline and glutathione metabolism being the most strongly-supported metabolic pathways associated with increased cold tolerance. We discuss several new targets in the study of insect cold tolerance (e.g. dopamine signaling and Na+-driven transport), but many previously identified candidate genes and pathways (e.g. heat shock proteins, Ca2+ signaling, and ROS detoxification) were also identified in the present study, and our results are thus consistent with and extend the current understanding of the mechanisms of insect chilling tolerance. PMID:27357258

Adaptation of the xylose fermenting yeast Saccharomyces cerevisiae F12 for improving ethanol production in different fed-batch SSF processes.

PubMed

Tomás-Pejó, E; Ballesteros, M; Oliva, J M; Olsson, L

2010-11-01

An efficient fermenting microorganism for bioethanol production from lignocellulose is highly tolerant to the inhibitors released during pretreatment and is able to ferment efficiently both glucose and xylose. In this study, directed evolution was employed to improve the xylose fermenting Saccharomyces cerevisiae F12 strain for bioethanol production at high substrate loading. Adapted and parental strains were compared with respect to xylose consumption and ethanol production. Adaptation led to an evolved strain more tolerant to the toxic compounds present in the medium. When using concentrated prehydrolysate from steam-pretreated wheat straw with high inhibitor concentration, an improvement of 65 and 20% in xylose consumption and final ethanol concentration, respectively, were achieved using the adapted strain. To address the need of high substrate loadings, fed-batch SSF experiments were performed and an ethanol concentration as high as 27.4 g/l (61% of the theoretical) was obtained with 11.25% (w/w) of water insoluble solids (WIS).

Effect of a low glycemic index compared with a conventional healthy diet on polycystic ovary syndrome.

PubMed

Marsh, Kate A; Steinbeck, Katharine S; Atkinson, Fiona S; Petocz, Peter; Brand-Miller, Jennie C

2010-07-01

Women with polycystic ovarian syndrome (PCOS) are intrinsically insulin resistant and have a high risk of cardiovascular disease and type 2 diabetes. Weight loss improves risk factors, but the optimal diet composition is unknown. Low-glycemic index (low-GI) diets are recommended without evidence of their clinical effectiveness. We compared changes in insulin sensitivity and clinical outcomes after similar weight losses after consumption of a low-GI diet compared with a conventional healthy diet in women with PCOS. We assigned overweight and obese premenopausal women with PCOS (n = 96) to consume either an ad libitum low-GI diet or a macronutrient-matched healthy diet and followed the women for 12 mo or until they achieved a 7% weight loss. We compared changes in whole-body insulin sensitivity, which we assessed using the insulin sensitivity index derived from the oral-glucose-tolerance test (ISI(OGTT)); glucose tolerance; body composition; plasma lipids; reproductive hormones; health-related quality of life; and menstrual cycle regularity. The attrition rate was high in both groups (49%). Among completers, ISI(OGTT) improved more with the low-GI diet than with the conventional healthy diet (mean +/- SEM: 2.2 +/- 0.7 compared with 0.7 +/- 0.6, respectively; P = 0.03). There was a significant diet-metformin interaction (P = 0.048), with greater improvement in ISI(OGTT) among women prescribed both metformin and the low-GI diet. Compared with women who consumed the conventional healthy diet, more women who consumed the low-GI diet showed improved menstrual cyclicity (95% compared with 63%, respectively; P = 0.03). Among the biochemical measures, only serum fibrinogen concentrations showed significant differences between diets (P < 0.05). To the best of our knowledge, this study provides the first objective evidence to justify the use of low-GI diets in the management of PCOS.

Structural equation models to estimate risk of infection and tolerance to bovine mastitis.

PubMed

Detilleux, Johann; Theron, Léonard; Duprez, Jean-Noël; Reding, Edouard; Humblet, Marie-France; Planchon, Viviane; Delfosse, Camille; Bertozzi, Carlo; Mainil, Jacques; Hanzen, Christian

2013-03-06

One method to improve durably animal welfare is to select, as reproducers, animals with the highest ability to resist or tolerate infection. To do so, it is necessary to distinguish direct and indirect mechanisms of resistance and tolerance because selection on these traits is believed to have different epidemiological and evolutionary consequences. We propose structural equation models with latent variables (1) to quantify the latent risk of infection and to identify, among the many potential mediators of infection, the few ones that influence it significantly and (2) to estimate direct and indirect levels of tolerance of animals infected naturally with pathogens. We applied the method to two surveys of bovine mastitis in the Walloon region of Belgium, in which we recorded herd management practices, mastitis frequency, and results of bacteriological analyses of milk samples. Structural equation models suggested that, among more than 35 surveyed herd characteristics, only nine (age, addition of urea in the rations, treatment of subclinical mastitis, presence of dirty liner, cows with hyperkeratotic teats, machine stripping, pre- and post-milking teat disinfection, and housing of milking cows in cubicles) were directly and significantly related to a latent measure of bovine mastitis, and that treatment of subclinical mastitis was involved in the pathway between post-milking teat disinfection and latent mastitis. These models also allowed the separation of direct and indirect effects of bacterial infection on milk productivity. Results suggested that infected cows were tolerant but not resistant to mastitis pathogens. We revealed the advantages of structural equation models, compared to classical models, for dissecting measurements of resistance and tolerance to infectious diseases, here bovine mastitis. Using our method, we identified nine major risk factors that were directly associated with an increased risk of mastitis and suggested that cows were tolerant but not resistant to mastitis. Selection should aim at improved resistance to infection by mastitis pathogens, although further investigations are needed due to the limitations of the data used in this study.

Dietary lecithin potentiates thermal tolerance and cellular stress protection of milk fish (Chanos Chanos) reared under low dose endosulfan-induced stress.

PubMed

Kumar, Neeraj; Minhas, P S; Ambasankar, K; Krishnani, K K; Rana, R S

2014-12-01

Endosulfan is an organochlorine pesticide commonly found in aquatic environments that has been found to reduce thermal tolerance of fish. Lipotropes such as the food additive, Lecithin has been shown to improve thermal tolerance in fish species. This study was conducted to evaluate the role of lipotropes (lecithin) for enhancing the thermal tolerance of Chanos chanos reared under sublethal low dose endosulfan-induced stress. Two hundred and twenty-five fish were distributed randomly into five treatments, each with three replicates. Four isocaloric and isonitrogenous diets were prepared with graded levels of lecithin: normal water and fed with control diet (En0/L0), endosulfan-treated water and fed with control diet (En/L0), endosulfan-treated water and fed with 1% (En/L1%), 1.5% (En/L 1.5%) and 2% (En/L 2%) lecithin supplemented feed. The endosulfan in treated water was maintained at the level of 1/40th of LC50 (0.52ppb). At the end of the five weeks, critical temperature maxima (CTmax), lethal temperature maxima (LTmax), critical temperature minima (CTmin) and lethal temperature minima (LTmin) were Determined. There was a significant (P<0.01) effect of dietary lecithin on temperature tolerance (CTmax, LTmax, CTmin and LTmin) of the groups fed with 1, 1.5 and 2% lecithin-supplemented diet compared to control and endosulfan-exposed groups. Positive correlations were observed between CT max and LTmax (R(2)=0.934) as well as between CTmin and LTmin (R(2)=0.9313). At the end of the thermal tolerance study, endosulfan-induced changes in cellular stress enzymes (Catalase, SOD and GST in liver and gill and neurotansmitter enzyme, brain AChE) were significantly (p<0.01) improved by dietary lecithin. We herein report the role of lecithin in enhancing the thermal tolerance and protection against cellular stress in fish exposed to an organochlorine pesticide. Copyright © 2014 Elsevier Ltd. All rights reserved.

New nanomicelle curcumin formulation for ocular delivery: improved stability, solubility, and ocular anti-inflammatory treatment.

PubMed

Li, Mengshuang; Xin, Meng; Guo, Chuanlong; Lin, Guiming; Wu, Xianggen

2017-11-01

A stable topical ophthalmic curcumin formulation with high solubility, stability, and efficacy is needed for pharmaceutical use in clinics. The objective of this article was to describe a novel curcumin containing a nanomicelle formulation using a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol (PVCL-PVA-PEG) graft copolymer. Nanomicelle curcumin was formulated and optimized and then further evaluated for in vitro cytotoxicity/in vivo ocular irritation, in vitro cellular uptake/in vivo corneal permeation, and in vitro antioxidant activity/in vivo anti-inflammatory efficacy. The solubility, chemical stability, and antioxidant activity were greatly improved after the encapsulation of the PVCL-PVA-PEG nanomicelles. The nanomicelle curcumin ophthalmic solution was simple to prepare and the nanomicelles are stable to the storage conditions, and it had good cellular tolerance. Nanomicelle curcumin also had excellent ocular tolerance in rabbits. The use of nanomicelles significantly improved in vitro cellular uptake and in vivo corneal permeation as well as improved anti-inflammatory efficacy when compared with a free curcumin solution. These findings indicate that nanomicelles could be promising topical delivery systems for the ocular administration of curcumin.

PRELIMINARY EVALUATION OF FeCrAl CLADDING AND U-Si FUEL FOR ACCIDENT TOLERANT FUEL CONCEPTS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hales, J. D.; Gamble, K. A.

2015-09-01

Since the accident at the Fukushima Daiichi Nuclear Power Station, enhancing the accident tolerance of light water reactors (LWRs) has become an important research topic. In particular, the community is actively developing enhanced fuels and cladding for LWRs to improve safety in the event of accidents in the reactor or spent fuel pools. Fuels with enhanced accident tolerance are those that, in comparison with the standard UO2-zirconium alloy system, can tolerate loss of active cooling in the reactor core for a considerably longer time period during design-basis and beyond design-basis events while maintaining or improving the fuel performance during normalmore » operations and operational transients. This paper presents early work in developing thermal and mechanical models for two materials that may have promise: U-Si for fuel, and FeCrAl for cladding. These materials would not necessarily be used together in the same fuel system, but individually have promising characteristics. BISON, the finite element-based fuel performance code in development at Idaho National Laboratory, was used to compare results from normal operation conditions with Zr-4/UO2 behavior. In addition, sensitivity studies are presented for evaluating the relative importance of material parameters such as ductility and thermal conductivity in FeCrAl and U-Si in order to provide guidance on future experiments for these materials.« less

High Tolerance to Iron Contamination in Lead Halide Perovskite Solar Cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Poindexter, Jeremy R.; Hoye, Robert L. Z.; Nienhaus, Lea

The relationship between charge-carrier lifetime and the tolerance of lead halide perovskite (LHP) solar cells to intrinsic point defects has drawn much attention by helping to explain rapid improvements in device efficiencies. However, little is known about how charge-carrier lifetime and solar cell performance in LHPs are affected by extrinsic defects (i.e., impurities), including those that are common in manufacturing environments and known to introduce deep levels in other semiconductors. Here, we evaluate the tolerance of LHP solar cells to iron introduced via intentional contamination of the feedstock and examine the root causes of the resulting efficiency losses. We findmore » that comparable efficiency losses occur in LHPs at feedstock iron concentrations approximately 100 times higher than those in p-type silicon devices. Photoluminescence measurements correlate iron concentration with nonradiative recombination, which we attribute to the presence of deep-level iron interstitials, as calculated from first-principles, as well as iron-rich particles detected by synchrotron-based X-ray fluorescence microscopy. At moderate contamination levels, we witness prominent recovery of device efficiencies to near-baseline values after biasing at 1.4 V for 60 s in the dark. We theorize that this temporary effect arises from improved charge-carrier collection enhanced by electric fields strengthened from ion migration toward interfaces. Lastly, our results demonstrate that extrinsic defect tolerance contributes to high efficiencies in LHP solar cells, which inspires further investigation into potential large-scale manufacturing cost savings as well as the degree of overlap between intrinsic and extrinsic defect tolerance in LHPs and 'perovskite-inspired' lead-free stable alternatives.« less

Effect of the absence of the CcpA gene on growth, metabolic production, and stress tolerance in Lactobacillus delbrueckii ssp. bulgaricus.

PubMed

Li, C; Sun, J W; Zhang, G F; Liu, L B

2016-01-01

The catabolite control protein A (CcpA) is a kind of multi-effect regulatory protein. In the study, the effect of the inactivation of CcpA and aerobic conditions on the growth, metabolic production, and stress tolerance to heat, oxidative, and cold stresses in Lactobacillus delbrueckii ssp. bulgaricus was investigated. Results showed that inactivation of CcpA distinctly hindered growth. Total lactic acid concentration was significantly lower in aerobiosis for both strains and was lower for the mutant strain than L. bulgaricus. Acetic acid production from the mutant strain was higher than L. bulgaricus in aerobiosis compared with anaerobiosis. Enzyme activities, lactate dehydrogenase (LDH), phosphate fructose kinase (PFK), pyruvate kinase (PK), and pyruvic dehydrogenase (PDH), were significantly lower in the mutant strain than L. bulgaricus. The diameters of inhibition zone were 13.59 ± 0.02 mm and 9.76 ± 0.02 mm for L. bulgaricus in anaerobiosis and aerobiosis, respectively; and 8.12 ± 0.02 mm and 7.38 ± 0.02 mm for the mutant in anaerobiosis and aerobiosis, respectively. For both strains, cells grown under aerobic environment possess more stress tolerance. This is the first study in which the CcpA-negative mutant of L. bulgaricus is constructed and the effect of aerobic growth on stress tolerance of L. bulgaricus is evaluated. Although aerobic cultivation does not significantly improve growth, it does improve stress tolerance. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

High Tolerance to Iron Contamination in Lead Halide Perovskite Solar Cells

DOE PAGES

Poindexter, Jeremy R.; Hoye, Robert L. Z.; Nienhaus, Lea; ...

2017-06-28

The relationship between charge-carrier lifetime and the tolerance of lead halide perovskite (LHP) solar cells to intrinsic point defects has drawn much attention by helping to explain rapid improvements in device efficiencies. However, little is known about how charge-carrier lifetime and solar cell performance in LHPs are affected by extrinsic defects (i.e., impurities), including those that are common in manufacturing environments and known to introduce deep levels in other semiconductors. Here, we evaluate the tolerance of LHP solar cells to iron introduced via intentional contamination of the feedstock and examine the root causes of the resulting efficiency losses. We findmore » that comparable efficiency losses occur in LHPs at feedstock iron concentrations approximately 100 times higher than those in p-type silicon devices. Photoluminescence measurements correlate iron concentration with nonradiative recombination, which we attribute to the presence of deep-level iron interstitials, as calculated from first-principles, as well as iron-rich particles detected by synchrotron-based X-ray fluorescence microscopy. At moderate contamination levels, we witness prominent recovery of device efficiencies to near-baseline values after biasing at 1.4 V for 60 s in the dark. We theorize that this temporary effect arises from improved charge-carrier collection enhanced by electric fields strengthened from ion migration toward interfaces. Lastly, our results demonstrate that extrinsic defect tolerance contributes to high efficiencies in LHP solar cells, which inspires further investigation into potential large-scale manufacturing cost savings as well as the degree of overlap between intrinsic and extrinsic defect tolerance in LHPs and 'perovskite-inspired' lead-free stable alternatives.« less

Durum wheat dehydrin (DHN-5) confers salinity tolerance to transgenic Arabidopsis plants through the regulation of proline metabolism and ROS scavenging system.

PubMed

Saibi, Walid; Feki, Kaouthar; Ben Mahmoud, Rihem; Brini, Faiçal

2015-11-01

The wheat dehydrin (DHN-5) gives birth to salinity tolerance to transgenic Arabidopsis plants by the regulation of proline metabolism and the ROS scavenging system. Dehydrins (DHNs) are involved in plant abiotic stress tolerance. In this study, we reported that salt tolerance of transgenic Arabidopsis plants overexpressing durum wheat dehydrin (DHN-5) was closely related to the activation of the proline metabolism enzyme (P5CS) and some antioxidant biocatalysts. Indeed, DHN-5 improved P5CS activity in the transgenic plants generating a significant proline accumulation. Moreover, salt tolerance of Arabidopsis transgenic plants was accompanied by an excellent activation of antioxidant enzymes like catalase (CAT), superoxide dismutase (SOD) and peroxide dismutase (POD) and generation of a lower level of hydrogen peroxide (H2O2) in leaves compared to the wild-type plants. The enzyme activities were enhanced in these transgenic plants in the presence of exogenous proline. Nevertheless, proline accumulation was slightly reduced in transgenic plants promoting chlorophyll levels. All these results suggest the crucial role of DHN-5 in response to salt stress through the activation of enzymes implicated in proline metabolism and in ROS scavenging enzymes.

Improved ethanol tolerance of Saccharomyces cerevisiae in mixed cultures with Kluyveromyces lactis on high-sugar fermentation.

PubMed

Yamaoka, Chizuru; Kurita, Osamu; Kubo, Tomoko

2014-12-01

The influence of non-Saccharomyces yeast, Kluyveromyces lactis, on metabolite formation and the ethanol tolerance of Saccharomyces cerevisiae in mixed cultures was examined on synthetic minimal medium containing 20% glucose. In the late stage of fermentation after the complete death of K. lactis, S. cerevisiae in mixed cultures was more ethanol-tolerant than that in pure culture. The chronological life span of S. cerevisiae was shorter in pure culture than mixed cultures. The yeast cells of the late stationary phase both in pure and mixed cultures had a low buoyant density with no significant difference in the non-quiescence state between both cultures. In mixed cultures, the glycerol contents increased and the alanine contents decreased when compared with the pure culture of S. cerevisiae. The distinctive intracellular amino acid pool concerning its amino acid concentrations and its amino acid composition was observed in yeast cells with different ethanol tolerance in the death phase. Co-cultivation of K. lactis seems to prompt S. cerevisiae to be ethanol tolerant by forming opportune metabolites such as glycerol and alanine and/or changing the intracellular amino acid pool. Copyright © 2014 Elsevier GmbH. All rights reserved.

Hypoxia tolerance and responses to hypoxic stress during heart and skeletal muscle inflammation in Atlantic salmon (Salmo salar).

PubMed

Lund, Morten; Krudtaa Dahle, Maria; Timmerhaus, Gerrit; Alarcon, Marta; Powell, Mark; Aspehaug, Vidar; Rimstad, Espen; Jørgensen, Sven Martin

2017-01-01

Heart and skeletal muscle inflammation (HSMI) is associated with Piscine orthoreovirus (PRV) infection and is an important disease in Atlantic salmon (Salmo salar) aquaculture. Since PRV infects erythrocytes and farmed salmon frequently experience environmental hypoxia, the current study examined mutual effects of PRV infection and hypoxia on pathogenesis and fish performance. Furthermore, effects of HSMI on hypoxia tolerance, cardiorespiratory performance and blood oxygen transport were studied. A cohabitation trial including PRV-infected post-smolts exposed to periodic hypoxic stress (4 h of 40% O2; PRV-H) at 4, 7 and 10 weeks post-infection (WPI) and infected fish reared under normoxic conditions (PRV) was conducted. Periodic hypoxic stress did not influence infection levels or histopathological changes in the heart. Individual incipient lethal oxygen saturation (ILOS) was examined using a standardized hypoxia challenge test (HCT). At 7 WPI, i.e. peak level of infection, both PRV and PRV-H groups exhibited reduced hypoxia tolerance compared to non-infected fish. Three weeks later (10 WPI), during peak levels of pathological changes, reduced hypoxia tolerance was still observed for the PRV group while PRV-H performed equal to non-infected fish, implying a positive effect of the repeated exposure to hypoxic stress. This was in line with maximum heart rate (fHmax) measurements, showing equal performance of PRV-H and non-infected groups, but lower fHmax above 19°C as well as lower temperature optimum (Topt) for aerobic scope for PRV, suggesting reduced cardiac performance and thermal tolerance. In contrast, the PRV-H group had reduced hemoglobin-oxygen affinity compared to non-infected fish. In conclusion, Atlantic salmon suffering from HSMI have reduced hypoxia tolerance and cardiac performance, which can be improved by preconditioning fish to transient hypoxic stress episodes.

Hypoxia tolerance and responses to hypoxic stress during heart and skeletal muscle inflammation in Atlantic salmon (Salmo salar)

PubMed Central

Krudtaa Dahle, Maria; Timmerhaus, Gerrit; Alarcon, Marta; Powell, Mark; Aspehaug, Vidar; Rimstad, Espen; Jørgensen, Sven Martin

2017-01-01

Heart and skeletal muscle inflammation (HSMI) is associated with Piscine orthoreovirus (PRV) infection and is an important disease in Atlantic salmon (Salmo salar) aquaculture. Since PRV infects erythrocytes and farmed salmon frequently experience environmental hypoxia, the current study examined mutual effects of PRV infection and hypoxia on pathogenesis and fish performance. Furthermore, effects of HSMI on hypoxia tolerance, cardiorespiratory performance and blood oxygen transport were studied. A cohabitation trial including PRV-infected post-smolts exposed to periodic hypoxic stress (4 h of 40% O2; PRV-H) at 4, 7 and 10 weeks post-infection (WPI) and infected fish reared under normoxic conditions (PRV) was conducted. Periodic hypoxic stress did not influence infection levels or histopathological changes in the heart. Individual incipient lethal oxygen saturation (ILOS) was examined using a standardized hypoxia challenge test (HCT). At 7 WPI, i.e. peak level of infection, both PRV and PRV-H groups exhibited reduced hypoxia tolerance compared to non-infected fish. Three weeks later (10 WPI), during peak levels of pathological changes, reduced hypoxia tolerance was still observed for the PRV group while PRV-H performed equal to non-infected fish, implying a positive effect of the repeated exposure to hypoxic stress. This was in line with maximum heart rate (fHmax) measurements, showing equal performance of PRV-H and non-infected groups, but lower fHmax above 19°C as well as lower temperature optimum (Topt) for aerobic scope for PRV, suggesting reduced cardiac performance and thermal tolerance. In contrast, the PRV-H group had reduced hemoglobin-oxygen affinity compared to non-infected fish. In conclusion, Atlantic salmon suffering from HSMI have reduced hypoxia tolerance and cardiac performance, which can be improved by preconditioning fish to transient hypoxic stress episodes. PMID:28700748

Effect of resin on impact damage tolerance of graphite/epoxy laminates

NASA Technical Reports Server (NTRS)

Williams, J. G.; Rhodes, M. D.

1982-01-01

Twenty-four different epoxy resin systems were evaluated by a variety of test techniques to identify materials that exhibited improved impact damage tolerance in graphite/epoxy composite laminates. Forty-eight-ply composite panels of five of the material systems were able to sustain 100 m/s impact by a 1.27-cm-diameter aluminum projectile while statically loaded to strains of 0.005. Of the five materials with the highest tolerance to impact, two had elastomeric additives, two had thermoplastic additives, and one had a vinyl modifier; all the five systems used bisphenol A as the base resin. An evaluation of test results shows that the laminate damage tolerance is largely determined by the resin tensile properties, and that improvements in laminate damage tolerance are not necessarily made at the expense of room-temperature mechanical properties. The results also suggest that a resin volume fraction of 40 percent or greater may be required to permit the plastic flow between fibers necessary for improved damage tolerance.

Overexpression of monoubiquitin improves photosynthesis in transgenic tobacco plants following high temperature stress.

PubMed

Tian, Fengxia; Gong, Jiangfeng; Zhang, Jin; Feng, Yanan; Wang, Guokun; Guo, Qifang; Wang, Wei

2014-09-01

The ubiquitin/26S proteasome system (Ub/26S) is implicated in abiotic stress responses in plants. In this paper, transgenic tobacco plants overexpressing Ta-Ub2 from wheat were used to study the functions of Ub in the improvement of photosynthesis under high temperature (45°C) stress. We observed higher levels of Ub conjugates in transgenic plants under high temperature stress conditions compared to wild type (WT) as a result of the constitutive overexpression of Ta-Ub2, suggesting increased protein degradation by the 26S proteasome system under high temperature stress. Overexpressing Ub increased the photosynthetic rate (Pn) of transgenic tobacco plants, consistent with the improved ATPase activity in the thylakoid membrane and enhanced efficiency of PSII photochemistry. The higher D1 protein levels following high temperature stress in transgenic plants than WT were also observed. These findings imply that Ub may be involved in tolerance of photosynthesis to high temperature stress in plants. Compared with WT, the transgenic plants showed lower protein carbonylation and malondialdehyde (MDA) levels, less reactive oxygen species (ROS) accumulation, but higher antioxidant enzyme activity under high temperature stress. These findings suggest that the improved antioxidant capacity of transgenic plants may be one of the most important mechanisms underlying Ub-regulated high temperature tolerance. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Recent Advances in Utilizing Transcription Factors to Improve Plant Abiotic Stress Tolerance by Transgenic Technology

PubMed Central

Wang, Hongyan; Wang, Honglei; Shao, Hongbo; Tang, Xiaoli

2016-01-01

Agricultural production and quality are adversely affected by various abiotic stresses worldwide and this will be exacerbated by the deterioration of global climate. To feed a growing world population, it is very urgent to breed stress-tolerant crops with higher yields and improved qualities against multiple environmental stresses. Since conventional breeding approaches had marginal success due to the complexity of stress tolerance traits, the transgenic approach is now being popularly used to breed stress-tolerant crops. So identifying and characterizing the critical genes involved in plant stress responses is an essential prerequisite for engineering stress-tolerant crops. Far beyond the manipulation of single functional gene, engineering certain regulatory genes has emerged as an effective strategy now for controlling the expression of many stress-responsive genes. Transcription factors (TFs) are good candidates for genetic engineering to breed stress-tolerant crop because of their role as master regulators of many stress-responsive genes. Many TFs belonging to families AP2/EREBP, MYB, WRKY, NAC, bZIP have been found to be involved in various abiotic stresses and some TF genes have also been engineered to improve stress tolerance in model and crop plants. In this review, we take five large families of TFs as examples and review the recent progress of TFs involved in plant abiotic stress responses and their potential utilization to improve multiple stress tolerance of crops in the field conditions. PMID:26904044

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sevik, James; Wallner, Thomas; Pamminger, Michael

The efficiency improvement and emissions reduction potential of lean and exhaust gas recirculation (EGR)-dilute operation of spark-ignition gasoline engines is well understood and documented. However, dilute operation is generally limited by deteriorating combustion stability with increasing inert gas levels. The combustion stability decreases due to reduced mixture flame speeds resulting in significantly increased combustion initiation periods and burn durations. A study was designed and executed to evaluate the potential to extend lean and EGR-dilute limits using a low-energy transient plasma ignition system. The low-energy transient plasma was generated by nanosecond pulses and its performance compared to a conventional transistorized coilmore » ignition (TCI) system operated on an automotive, gasoline direct-injection (GDI) single-cylinder research engine. The experimental assessment was focused on steady-state experiments at the part load condition of 1500 rpm 5.6 bar indicated mean effective pressure (IMEP), where dilution tolerance is particularly critical to improving efficiency and emission performance. Experimental results suggest that the energy delivery process of the low-energy transient plasma ignition system significantly improves part load dilution tolerance by reducing the early flame development period. Statistical analysis of relevant combustion metrics was performed in order to further investigate the effects of the advanced ignition system on combustion stability. Results confirm that at select operating conditions EGR tolerance and lean limit could be improved by as much as 20% (from 22.7 to 27.1% EGR) and nearly 10% (from λ = 1.55 to 1.7) with the low-energy transient plasma ignition system.« less

A double-masked, placebo-controlled study of fluoxetine for hypochondriasis.

PubMed

Fallon, Brian A; Petkova, Eva; Skritskaya, Natalia; Sanchez-Lacay, Arturo; Schneier, Franklin; Vermes, Donna; Cheng, Jianfeng; Liebowitz, Michael R

2008-12-01

This study assessed the efficacy, durability, and tolerability of fluoxetine for hypochondriasis, a disorder for which controlled pharmacological trials are scarce. Fifty-seven patients with hypochondriasis were enrolled: 12 discontinued during the placebo run-in, and 45 were randomized to either fluoxetine or placebo for 12 weeks (acute treatment). Responder status was defined as a Clinical Global Impression rating for hypochondriasis of much or very much improved. Secondary outcome measures included severity of hypochondriasis, somatization, anxiety, and depression. Responders to acute treatment entered a 12-week maintenance phase to week 24. Sustained responders at week 24 entered a 12-week double-masked discontinuation phase. Primary analysis used the intent-to-treat sample. More patients responded with improvement in hypochondriasis when given fluoxetine compared with placebo, starting at week 8 (50.0% vs 19.0%, P = 0.03) and continuing to week 12 (62.5% vs 33.3%, P = 0.05). Mean dose at week 12 dose was 51.4 mg (SD, +/-23 mg). The acute treatment response was maintained to week 24 with more responders in the fluoxetine compared with the placebo group (54.2% vs 23.8%, P = 0.04). Significant improvement was not noted on the continuous secondary outcomes measures of hypochondriasis, with the exception of the Clinical Global Impression hypochondriasis severity scale at week 24. Likelihood of response was not associated with severity of psychiatric comorbidity. Durability of response after controlled drug discontinuation could not be reasonably assessed, given the small sample size of patients who entered the discontinuation phase (n = 10). Fluoxetine was well tolerated, with no significant differences in discontinuation due to side effects between treatment groups. Fluoxetine is a moderately effective and well-tolerated treatment for hypochondriasis.

Comparative study between: Carboxytherapy, platelet-rich plasma, and tripolar radiofrequency, their efficacy and tolerability in striae distensae.

PubMed

Ahmed, Naglaa A; Mostafa, Osama M

2018-06-19

Striae distensae are very common cutaneous disorders that produce great psychological stress for women. measure and compare between efficacy and tolerability of three modalities for treatment of striae distensae. Forty-five female patients with striae distensae were randomly selected from the outpatient dermatology clinics of Al-Zahra university Hospital within 6 months period. Patients divided into three groups according to the therapeutic modalities were used. Group A: treated with carboxytherapy using carbon dioxide (CO2) injection, Group B: where patients were treated with intradermal injection of autologous platelet-rich plasma (PRP), and Group C: where we used tripolar radiofrequency (RF) for treatment. All treated groups showed overall clinical improvement as regards the width, texture, and overall improvement after treatment (P > .05), with no statistically significant differences between the three groups. Patient's satisfaction was statistically significantly better in both group C (93.33%) and group A (80%) while group B (53.33%) was less with minimal side effects such as pain and ecchymosis, which were more frequent in group B than the other two groups; but with no statistically significance differences both groups A and C were effective with no significant differences in both types of striae and in any site of the body but group B is significantly more effective on striae rubra on trunk, with better improvement of lesions texture. The three modalities of treatments proved to be effective clinically and histopathologically in treating both types of striae, which were well tolerated by the patients with minimal, transient side effects and our study results gave us guidelines for their clinical application. © 2018 Wiley Periodicals, Inc.

A randomized, comparative, open-label study of efficacy and tolerability of alfuzosin, tamsulosin and silodosin in benign prostatic hyperplasia

PubMed Central

Manjunatha, R.; Pundarikaksha, H. P.; Madhusudhana, H. R.; Amarkumar, J.; Hanumantharaju, B. K.

2016-01-01

Objectives: Benign prostatic hyperplasia (BPH) is a common and progressive disease affecting elderly males, often associated with lower urinary tract symptoms (LUTS). α1-blockers are the mainstay in symptomatic therapy of BPH. Because of their greater uroselectivity and minimal hemodynamic effects, alfuzosin, tamsulosin, and silodosin are generally preferred. The aim of this study was to compare the efficacy and tolerability of alfuzosin, tamsulosin, and silodosin in patients with BPH and LUTS. Methods: Ninety subjects with BPH and LUTS were randomized into three groups of thirty in each, to receive alfuzosin sustained release (SR) 10 mg, tamsulosin 0.4 mg, or silodosin 8 mg for 12 weeks. The primary outcome measure was a change in the International Prostate Symptom Score (IPSS), and the secondary outcome measures were changes in individual subjective symptom scores, quality of life score (QLS), and peak flow rate (Qmax) from baseline. The treatment response was monitored at 2, 4, 8, and 12 weeks. Results: IPSS improved by 88.18%, 72.12%, and 82.23% in alfuzosin SR, tamsulosin and silodosin groups (P < 0.001) at 12 weeks. Improvement in QLS was >75% in all the three groups (P < 0.001). A significant improvement in Qmax was seen with alfuzosin and tamsulosin (P = 0.025 and P < 0.001) but not with silodosin (P = 0.153). However, the intergroup differences in IPSS, QLS, and Qmax were not significant. Ejaculatory dysfunction was more common with silodosin and corrected QT (QTc) prolongation occurred only with alfuzosin (two subjects) and tamsulosin (three subjects). Conclusion: Alfuzosin, tamsulosin, and silodosin showed similar efficacy in improvement of LUTS secondary to BPH, with good tolerability, acceptability, and minimum hemodynamic adverse effects. Alfuzosin, tamsulosin, and silodosin are comparable in efficacy in symptomatic management of BPH. The occurrence of QTc prolongation in three subjects with tamsulosin in the present study is an unexpected adverse event as there are no reports of QTc prolongation with tamsulosin in any of the previous studies. PMID:27127315

Generation of a platform strain for ionic liquid tolerance using adaptive laboratory evolution

DOE PAGES

Mohamed, Elsayed T.; Wang, Shizeng; Lennen, Rebecca M.; ...

2017-11-16

There is a need to replace petroleum-derived with sustainable feedstocks for chemical production. Certain biomass feedstocks can meet this need as abundant, diverse, and renewable resources. Specific ionic liquids (ILs) can play a role in this process as promising candidates for chemical pretreatment and deconstruction of plant-based biomass feedstocks as they efficiently release carbohydrates which can be fermented. However, the most efficient pretreatment ILs are highly toxic to biological systems, such as microbial fermentations, and hinder subsequent bioprocessing of fermentative sugars obtained from IL-treated biomass. To generate strains capable of tolerating residual ILs present in treated feedstocks, a tolerance adaptivemore » laboratory evolution (TALE) approach was developed and utilized to improve growth of two different Escherichia coli strains, DH1 and K-12 MG1655, in the presence of two different ionic liquids, 1-ethyl-3-methylimidazolium acetate ([C 2C 1Im][OAc] ) and 1-butyl-3-methylimidazolium chloride ([C 4C 1Im]Cl). For multiple parallel replicate populations of E. coli, cells were repeatedly passed to select for improved fitness over the course of approximately 40 days. Clonal isolates were screened and the best performing isolates were subjected to whole genome sequencing. The most prevalent mutations in tolerant clones occurred in transport processes related to the functions of mdtJI, a multidrug efflux pump, and yhdP, an uncharacterized transporter. Additional mutations were enriched in processes such as transcriptional regulation and nucleotide biosynthesis. Finally, the best-performing strains were compared to previously characterized tolerant strains and showed superior performance in tolerance of different IL and media combinations (i.e., cross tolerance) with robust growth at 8.5% (w/v) and detectable growth up to 11.9% (w/v) [C 2C 1Im][OAc]. The generated strains thus represent the best performing platform strains available for bioproduction utilizing IL-treated renewable substrates, and the TALE method was highly successful in overcoming the general issue of substrate toxicity and has great promise for use in tolerance engineering.« less

Generation of a platform strain for ionic liquid tolerance using adaptive laboratory evolution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mohamed, Elsayed T.; Wang, Shizeng; Lennen, Rebecca M.

There is a need to replace petroleum-derived with sustainable feedstocks for chemical production. Certain biomass feedstocks can meet this need as abundant, diverse, and renewable resources. Specific ionic liquids (ILs) can play a role in this process as promising candidates for chemical pretreatment and deconstruction of plant-based biomass feedstocks as they efficiently release carbohydrates which can be fermented. However, the most efficient pretreatment ILs are highly toxic to biological systems, such as microbial fermentations, and hinder subsequent bioprocessing of fermentative sugars obtained from IL-treated biomass. To generate strains capable of tolerating residual ILs present in treated feedstocks, a tolerance adaptivemore » laboratory evolution (TALE) approach was developed and utilized to improve growth of two different Escherichia coli strains, DH1 and K-12 MG1655, in the presence of two different ionic liquids, 1-ethyl-3-methylimidazolium acetate ([C 2C 1Im][OAc] ) and 1-butyl-3-methylimidazolium chloride ([C 4C 1Im]Cl). For multiple parallel replicate populations of E. coli, cells were repeatedly passed to select for improved fitness over the course of approximately 40 days. Clonal isolates were screened and the best performing isolates were subjected to whole genome sequencing. The most prevalent mutations in tolerant clones occurred in transport processes related to the functions of mdtJI, a multidrug efflux pump, and yhdP, an uncharacterized transporter. Additional mutations were enriched in processes such as transcriptional regulation and nucleotide biosynthesis. Finally, the best-performing strains were compared to previously characterized tolerant strains and showed superior performance in tolerance of different IL and media combinations (i.e., cross tolerance) with robust growth at 8.5% (w/v) and detectable growth up to 11.9% (w/v) [C 2C 1Im][OAc]. The generated strains thus represent the best performing platform strains available for bioproduction utilizing IL-treated renewable substrates, and the TALE method was highly successful in overcoming the general issue of substrate toxicity and has great promise for use in tolerance engineering.« less

Comparative analysis of the response and gene regulation in cold resistant and susceptible tea plants

PubMed Central

Pan, Cheng; Wang, Yiwei; Kong, Lei; Jiang, Huiguang; Xu, Yiqun; Wang, Wenzhi; Pan, Yuting; Li, Yeyun; Jiang, Changjun

2017-01-01

Cold environment is the main constraint for tea plants (Camellia sinensis) distribution and tea farming. We identified two tea cultivars, called var. sinensis cv. Shuchazao (SCZ) with a high cold-tolerance and var. assamica cv. Yinghong9 (YH9) with low cold-tolerance. To better understand the response mechanism of tea plants under cold stress for improving breeding, we compared physiological and biochemical responses, and associated genes expression in response to 7-day and 14-day cold acclimation, followed by 7-day de-acclimation in these two tea cultivars. We found that the low EL50, low Fv/Fm, and high sucrose and raffinose accumulation are responsible for higher cold tolerance in SCZ comparing with YH9. We then measured the expression of 14 key homologous genes, known as involved in these responses in other plants, for each stages of treatment in both cultivars using RT-qPCR. Our results suggested that the increased expression of CsCBF1 and CsDHNs coupling with the accumulation of sucrose play key roles in conferring higher cold resistance in SCZ. Our findings have revealed key genes regulation responsible for cold resistance, which help to understand the cold-resistant mechanisms and guide breeding in tea plants. PMID:29211766

Comparative analysis of the response and gene regulation in cold resistant and susceptible tea plants.

PubMed

Ban, Qiuyan; Wang, Xuewen; Pan, Cheng; Wang, Yiwei; Kong, Lei; Jiang, Huiguang; Xu, Yiqun; Wang, Wenzhi; Pan, Yuting; Li, Yeyun; Jiang, Changjun

2017-01-01

Cold environment is the main constraint for tea plants (Camellia sinensis) distribution and tea farming. We identified two tea cultivars, called var. sinensis cv. Shuchazao (SCZ) with a high cold-tolerance and var. assamica cv. Yinghong9 (YH9) with low cold-tolerance. To better understand the response mechanism of tea plants under cold stress for improving breeding, we compared physiological and biochemical responses, and associated genes expression in response to 7-day and 14-day cold acclimation, followed by 7-day de-acclimation in these two tea cultivars. We found that the low EL50, low Fv/Fm, and high sucrose and raffinose accumulation are responsible for higher cold tolerance in SCZ comparing with YH9. We then measured the expression of 14 key homologous genes, known as involved in these responses in other plants, for each stages of treatment in both cultivars using RT-qPCR. Our results suggested that the increased expression of CsCBF1 and CsDHNs coupling with the accumulation of sucrose play key roles in conferring higher cold resistance in SCZ. Our findings have revealed key genes regulation responsible for cold resistance, which help to understand the cold-resistant mechanisms and guide breeding in tea plants.

Enhanced Gene Expression Rather than Natural Polymorphism in Coding Sequence of the OsbZIP23 Determines Drought Tolerance and Yield Improvement in Rice Genotypes

PubMed Central

Dey, Avishek; Samanta, Milan Kumar; Gayen, Srimonta; Sen, Soumitra K.; Maiti, Mrinal K.

2016-01-01

Drought is one of the major limiting factors for productivity of crops including rice (Oryza sativa L.). Understanding the role of allelic variations of key regulatory genes involved in stress-tolerance is essential for developing an effective strategy to combat drought. The bZIP transcription factors play a crucial role in abiotic-stress adaptation in plants via abscisic acid (ABA) signaling pathway. The present study aimed to search for allelic polymorphism in the OsbZIP23 gene across selected drought-tolerant and drought-sensitive rice genotypes, and to characterize the new allele through overexpression (OE) and gene-silencing (RNAi). Analyses of the coding DNA sequence (CDS) of the cloned OsbZIP23 gene revealed single nucleotide polymorphism at four places and a 15-nucleotide deletion at one place. The single-copy OsbZIP23 gene is expressed at relatively higher level in leaf tissues of drought-tolerant genotypes, and its abundance is more in reproductive stage. Cloning and sequence analyses of the OsbZIP23-promoter from drought-tolerant O. rufipogon and drought-sensitive IR20 cultivar showed variation in the number of stress-responsive cis-elements and a 35-nucleotide deletion at 5’-UTR in IR20. Analysis of the GFP reporter gene function revealed that the promoter activity of O. rufipogon is comparatively higher than that of IR20. The overexpression of any of the two polymorphic forms (1083 bp and 1068 bp CDS) of OsbZIP23 improved drought tolerance and yield-related traits significantly by retaining higher content of cellular water, soluble sugar and proline; and exhibited decrease in membrane lipid peroxidation in comparison to RNAi lines and non-transgenic plants. The OE lines showed higher expression of target genes-OsRab16B, OsRab21 and OsLEA3-1 and increased ABA sensitivity; indicating that OsbZIP23 is a positive transcriptional-regulator of the ABA-signaling pathway. Taken together, the present study concludes that the enhanced gene expression rather than natural polymorphism in coding sequence of OsbZIP23 is accountable for improved drought tolerance and yield performance in rice genotypes. PMID:26959651

Long-term use of neonatal helmet-CPAP: a case report.

PubMed

Doglioni, N; Micaglio, M; Zanardo, V; Trevisanuto, D

2009-12-01

In a recent short-term physiological study, we demonstrated a new continuous positive airway pressure (CPAP) system (neonatal helmet-CPAP) that could be a feasible device for managing preterm infants needing continuous distending pressure with better tolerability than nasal-CPAP. However, its application for a long-term period has never been reported in neonates. Here, we describe the use of neonatal helmet-CPAP in a neonate with persistent pulmonary hypertension of the newborn. Twenty minutes after neonatal helmet-CPAP placement, the baseline post-ductal tcSaO2 (66%) and alveolar-arterial gradient O2 improved from 66% and 648 mmHg to 100% and 465 mmHg, respectively. The neonatal helmet-CPAP was applied for 48 hours and was well-tolerated by the patient without complications. Long-term use of neonatal helmet-CPAP appears feasible and well-tolerated. Comparative trials are needed.

Fault-tolerant simple quantum-bit commitment unbreakable by individual attacks

NASA Astrophysics Data System (ADS)

Shimizu, Kaoru; Imoto, Nobuyuki

2002-03-01

This paper proposes a simple scheme for quantum-bit commitment that is secure against individual particle attacks, where a sender is unable to use quantum logical operations to manipulate multiparticle entanglement for performing quantum collective and coherent attacks. Our scheme employs a cryptographic quantum communication channel defined in a four-dimensional Hilbert space and can be implemented by using single-photon interference. For an ideal case of zero-loss and noiseless quantum channels, our basic scheme relies only on the physical features of quantum states. Moreover, as long as the bit-flip error rates are sufficiently small (less than a few percent), we can improve our scheme and make it fault tolerant by adopting simple error-correcting codes with a short length. Compared with the well-known Brassard-Crepeau-Jozsa-Langlois 1993 (BCJL93) protocol, our scheme is mathematically far simpler, more efficient in terms of transmitted photon number, and better tolerant of bit-flip errors.

In situ heavy ion irradiation studies of nanopore shrinkage and enhanced radiation tolerance of nanoporous Au

DOE PAGES

Li, Jin; Fan, Cuncai; Ding, Jie; ...

2017-01-03

High energy particle radiations induce severe microstructural damage in metallic materials. Nanoporous materials with a giant surface-to-volume ratio may alleviate radiation damage in irradiated metallic materials as free surface are defect sinks. We show, by using in situ Kr ion irradiation in a transmission electron microscope at room temperature, that nanoporous Au indeed has significantly improved radiation tolerance comparing with coarse-grained, fully dense Au. In situ studies show that nanopores can absorb and eliminate a large number of radiation-induced defect clusters. Meanwhile, nanopores shrink (self-heal) during radiation, and their shrinkage rate is pore size dependent. Furthermore, the in situ studiesmore » show dose-rate-dependent diffusivity of defect clusters. Our study sheds light on the design of radiation-tolerant nanoporous metallic materials for advanced nuclear reactor applications.« less

Tailoring the Oxidative Stress Tolerance of Clostridium tyrobutyricum CCTCC W428 by Introducing Trehalose Biosynthetic Capability.

PubMed

Wu, Qian; Zhu, Liying; Xu, Qing; Huang, He; Jiang, Ling; Yang, Shang-Tian

2017-10-11

Fermentations employing anaerobes always suffer from the restriction of stringent anaerobic conditions during the production of bulk and fine chemicals. This work aims to improve the oxidative stress tolerance of C. tyrobutyricum CCTCC W428, an ideal butyric-acid-producing anaerobe, via the introduction of trehalose biosynthesis capability. Compared with the wild type, the engineered strain showed a wider substrate spectrum, an improved metabolic profile, and a significantly increased specific growth rate upon aeration and acid challenge. Molecular simulation experiments indicated that CoA transferase maintained its native folded state when protected by the trehalose system. Furthermore, qRT-PCR was combined assays for acid-related enzyme activities under various conditions to verify the effects of trehalose. These results demonstrate that introducing a trehalose biosynthetic pathway, which is redundant for the metabolism of C. tyrobutyricum, can increase the robustness of the host to achieve a better oxidative resistance.

Directed evolution of an ultrastable carbonic anhydrase for highly efficient carbon capture from flue gas

DOE PAGES

Alvizo, Oscar; Nguyen, Luan J.; Savile, Christopher K.; ...

2014-11-03

Carbonic anhydrase (CA) is one of nature’s fastest enzymes and can dramatically improve the economics of carbon capture under demanding environments such as coal-fired power plants. The use of CA to accelerate carbon capture is limited by the enzyme’s sensitivity to the harsh process conditions. Using directed evolution, the properties of a β-class CA from Desulfovibrio vulgaris were dramatically enhanced. Iterative rounds of library design, library generation, and high-throughput screening identified highly stable CA variants that tolerate temperatures of up to 107 °C in the presence of 4.2 M alkaline amine solvent at pH >10.0. This increase in thermostability andmore » alkali tolerance translates to a 4,000,000-fold improvement over the natural enzyme. In conclusion, at pilot scale, the evolved catalyst enhanced the rate of CO2 absorption 25-fold compared with the noncatalyzed reaction.« less

Directed evolution of an ultrastable carbonic anhydrase for highly efficient carbon capture from flue gas

PubMed Central

Alvizo, Oscar; Nguyen, Luan J.; Savile, Christopher K.; Bresson, Jamie A.; Lakhapatri, Satish L.; Solis, Earl O. P.; Fox, Richard J.; Broering, James M.; Benoit, Michael R.; Zimmerman, Sabrina A.; Novick, Scott J.; Liang, Jack; Lalonde, James J.

2014-01-01

Carbonic anhydrase (CA) is one of nature’s fastest enzymes and can dramatically improve the economics of carbon capture under demanding environments such as coal-fired power plants. The use of CA to accelerate carbon capture is limited by the enzyme’s sensitivity to the harsh process conditions. Using directed evolution, the properties of a β-class CA from Desulfovibrio vulgaris were dramatically enhanced. Iterative rounds of library design, library generation, and high-throughput screening identified highly stable CA variants that tolerate temperatures of up to 107 °C in the presence of 4.2 M alkaline amine solvent at pH >10.0. This increase in thermostability and alkali tolerance translates to a 4,000,000-fold improvement over the natural enzyme. At pilot scale, the evolved catalyst enhanced the rate of CO2 absorption 25-fold compared with the noncatalyzed reaction. PMID:25368146

SU-E-T-760: Tolerance Design for Site-Specific Range in Proton Patient QA Process Using the Six Sigma Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lah, J; Shin, D; Kim, G

Purpose: To show how tolerance design and tolerancing approaches can be used to predict and improve the site-specific range in patient QA process in implementing the Six Sigma. Methods: In this study, patient QA plans were selected according to 6 site-treatment groups: head &neck (94 cases), spine (76 cases), lung (89 cases), liver (53 cases), pancreas (55 cases), and prostate (121 cases), treated between 2007 and 2013. We evaluated a model of the Six Sigma that determines allowable deviations in design parameters and process variables in patient-specific QA, where possible, tolerance may be loosened, then customized if it necessary tomore » meet the functional requirements. A Six Sigma problem-solving methodology is known as DMAIC phases, which are used stand for: Define a problem or improvement opportunity, Measure process performance, Analyze the process to determine the root causes of poor performance, Improve the process by fixing root causes, Control the improved process to hold the gains. Results: The process capability for patient-specific range QA is 0.65 with only ±1 mm of tolerance criteria. Our results suggested the tolerance level of ±2–3 mm for prostate and liver cases and ±5 mm for lung cases. We found that customized tolerance between calculated and measured range reduce that patient QA plan failure and almost all sites had failure rates less than 1%. The average QA time also improved from 2 hr to less than 1 hr for all including planning and converting process, depth-dose measurement and evaluation. Conclusion: The objective of tolerance design is to achieve optimization beyond that obtained through QA process improvement and statistical analysis function detailing to implement a Six Sigma capable design.« less

Real-time mapping of salt glands on the leaf surface of Cynodon dactylon L. using scanning electrochemical microscopy.

PubMed

Parthasarathy, Meera; Pemaiah, Brindha; Natesan, Ravichandran; Padmavathy, Saralla R; Pachiappan, Jayaraman

2015-02-01

Salt glands are specialized organelles present in the leaf tissues of halophytes, which impart salt-tolerance capability to the plant species. These glands are usually identified only by their morphology using conventional staining procedures coupled with optical microscopy. In this work, we have employed scanning electrochemical microscopy to identify the salt glands not only by their morphology but also by their salt excretion behavior. Bermuda grass (Cynodon dactylon L.) species was chosen for the study as they are known to be salt-tolerant and contain salt glands on leaf surfaces. Scanning electrochemical microscopy performed in sodium chloride medium in the presence and absence of potassium ferrocyanide as redox mediator, reveals the identity of salt glands. More insight into the ion expulsion behavior of these glands was obtained by mapping lateral and vertical variations in ion concentrations using surface impedance measurements which indicated five times higher resistance over the salt glands compared to the surrounding tissues and bulk solution. The protocol could be used to understand the developmental processes in plants grown in different soil/water conditions in order to improve salt tolerance of food crops by genetic engineering and hence improve their agricultural productivity.

Use of the ketogenic diet in the neonatal intensive care unit-Safety and tolerability.

PubMed

Thompson, Lindsey; Fecske, Erin; Salim, Mohammad; Hall, Ara

2017-02-01

Drug-resistant epilepsy poses a challenge in neonatal patients, especially those in the neonatal intensive care unit (NICU), who have various secondary comorbidities. We present results of four children with a history of drug-resistant epilepsy for whom a ketogenic diet was initiated and used in the NICU. A nonfasting induction into ketosis over 1-2 weeks was utilized, with gradual increases in the ketogenic ratio every 2-3 days. Data were collected retrospectively from a database, which included medical history, daily progress notes, relevant laboratory data, and imaging and diagnostic information. The ketogenic diet was well tolerated in all cases. The most common side effects observed were constipation, hypoglycemia, and weight loss. Serum β-hydroxybutyrate levels demonstrated improved reliability as a marker of ketosis when compared to urine ketones in this population. Perceived benefits to the infants included improved seizure control, increased alertness, and decreased need for invasive respiratory support. These cases demonstrate that the use of the ketogenic diet for treatment of neonatal encephalopathy and refractory epilepsy can be undertaken safely in the NICU and is well tolerated by carefully screened neonates and infants. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Overexpression of an aquaglyceroporin gene from Trichoderma harzianum improves water-use efficiency and drought tolerance in Nicotiana tabacum.

PubMed

Vieira, Pabline Marinho; Santos, Mirella Pupo; Andrade, Cristiana Moura; Souza-Neto, Otacílio Antônio; Ulhoa, Cirano José; Aragão, Francisco José Lima

2017-12-01

Aquaporins (AQPs) and aquaglyceroporins (AQGPs) are integral membrane proteins that mediate the transport of water and solutes, such as glycerol and urea, across membranes. AQP and AQGP genes represent a valuable tool for biotechnological improvement of plant tolerance to environmental stresses. We previously isolated a gene encoding for an aquaglyceroporin (ThAQGP), which was up-regulated in Trichoderma harzianum during interaction with the plant pathogen Fusarium solani. This gene was introduced into Nicotiana tabacum and plants were physiologically characterized. Under favorable growth conditions, transgenic progenies did not had differences in both germination and growth rates when compared to wild type. However, physiological responses under drought stress revealed that transgenic plants presented significantly higher transpiration rate, stomatal conductance, photosynthetic efficiency and faster turgor recovery than wild type. Quantitative RT-PCR analysis demonstrated the presence of ThAQGP transcripts in transgenic lines, showing the cause-effect relationship between the observed phenotype and the expression of the transgene. Our results underscore the high potential of T. harzianum as a source of genes with promising applications in transgenic plants tolerant to drought stress. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Overexpression of a glyoxalase gene, OsGly I, improves abiotic stress tolerance and grain yield in rice (Oryza sativa L.).

PubMed

Zeng, Zhengming; Xiong, Fangjie; Yu, Xiaohong; Gong, Xiaoping; Luo, Juntao; Jiang, Yudong; Kuang, Haochi; Gao, Bijun; Niu, Xiangli; Liu, Yongsheng

2016-12-01

Glyoxalase I (Gly I) is a component of the glyoxalase system which is involved in the detoxification of methylglyoxal, a byproduct of glycolysis. In the present study, a gene of rice (Oryza sativa L., cv. Nipponbare) encoding Gly I was cloned and characterized. The quantitative real-time PCR analysis indicated that rice Gly I (OsGly I) was ubiquitously expressed in root, stem, leaf, leaf sheath and spikelet with varying abundance. OsGly I was markedly upregulated in response to NaCl, ZnCl 2 and mannitol in rice seedlings. For further functional investigation, OsGly I was overexpressed in rice using Agrobacterium-mediated transformation. Transgenic rice lines exhibited increased glyoxalase enzyme activity, decreased methylglyoxal level and improved tolerance to NaCl, ZnCl 2 and mannitol compared to wild-type plants. Enhancement of stress tolerance in transgenic lines was associated with reduction of malondialdehyde content which was derived from cellular lipid peroxidation. In addition, the OsGly I-overexpression transgenic plants performed higher seed setting rate and yield. Collectively, these results indicate the potential of bioengineering the Gly I gene in crops. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Shrimp oil extracted from the shrimp processing waste reduces the development of insulin resistance and metabolic phenotypes in diet-induced obese rats.

PubMed

Nair, Sandhya; Gagnon, Jacques; Pelletier, Claude; Tchoukanova, Nadia; Zhang, Junzeng; Ewart, H Stephen; Ewart, K Vanya; Jiao, Guangling; Wang, Yanwen

2017-08-01

Diet-induced obesity, insulin resistance, impaired glucose tolerance, chronic inflammation, and oxidative stress represent the main features of type 2 diabetes mellitus. The present study was conducted to examine the efficacy and mechanisms of shrimp oil on glucose homeostasis in obese rats. Male CD rats fed a high-fat diet (52 kcal% fat) and 20% fructose drinking water were divided into 4 groups and treated with the dietary replacement of 0%, 10%, 15%, or 20% of lard with shrimp oil for 10 weeks. Age-matched rats fed a low-fat diet (10 kcal% fat) were used as the normal control. Rats on the high-fat diet showed impaired (p < 0.05) glucose tolerance and insulin resistance compared with rats fed the low-fat diet. Shrimp oil improved (p < 0.05) oral glucose tolerance, insulin response, and homeostatic model assessment-estimated insulin resistance index; decreased serum insulin, leptin, hemoglobin A1c, and free fatty acids; and increased adiponectin. Shrimp oil also increased (p < 0.05) antioxidant capacity and reduced oxidative stress and chronic inflammation. The results demonstrated that shrimp oil dose-dependently improved glycemic control in obese rats through multiple mechanisms.

ARTP mutation and genome shuffling of ABE fermentation symbiotic system for improvement of butanol production.

PubMed

Gu, Chunkai; Wang, Genyu; Mai, Shuai; Wu, Pengfei; Wu, Jianrong; Wang, Gehua; Liu, Hongjuan; Zhang, Jianan

2017-03-01

Butanol is an ideal renewable biofuel which possesses superior fuel properties. Previously, butanol-producing symbiotic system TSH06 was isolated in our lab, with microoxygen tolerance ability. To boost butanol yield for large-scale industrial production, TSH06 was used as parental strain and subjected to atmospheric and room temperature plasma (ARTP) and four rounds of genome shuffling (GS). ARTP mutant and GS strain were co-cultured with facultative anaerobic Bacillus cereus TSH2 to form a symbiotic system with microoxygen tolerance, which was then subjected to fermentation. Relative messenger RNA (mRNA) level of key enzyme gene was measured by real-time PCR. The highest butanol titer of TS4-30 reached 15.63 g/L, which was 34% higher than TSH06 (12.19 g/L). Compared with parental strain, mRNA of acid-forming gene in TS4-30 decreased in acidogenesis phase, while solvent-forming gene increased in solventogenesis phase. This gene expression pattern was consistent with high butanol yield and low acid level in TS4-30. In summary, symbiotic system TS4-30 was obtained with butanol titer improvement and microoxygen tolerance.

The long-term effect of zinc soil contamination on selected free amino acids playing an important role in plant adaptation to stress and senescence.

PubMed

Pavlíková, Daniela; Zemanová, Veronika; Procházková, Dagmar; Pavlík, Milan; Száková, Jiřina; Wilhelmová, Naďa

2014-02-01

Increased endogenous plant cytokinin (CK) content through transformation with an isopentyl transferase (ipt) gene has been associated with improved plant stress tolerance. The objective of this study is to determine amino acid changes associated with elevated CK production in ipt transgenic tobacco (Nicotiana tabacum L., cv. Wisconsin 38). Nontransformed (WT) and transformed tobacco plants with ipt gene controlled by senescence-activated promoter (SAG) were exposed to zinc soil contamination (tested levels Zn1=250, Zn2=500, Zn3=750 mg kg(-1) soil). The Zn effect on plant stress metabolism resulted in changes in levels of selected free amino acids playing an important role in adaptation to stress and plant senescence (alanine, leucine, proline, methionine and γ-aminobutyrate) and differed for transformed and nontransformed tobacco plants. Analyses of amino acids confirmed that SAG tobacco plants had improved zinc tolerance compared with the WT plants. The enhanced Zn tolerance of SAG plants was associated with the maintenance of accumulation of proline, methionine and γ-aminobutyrate. The concentrations of leucine and alanine did not show significant differences between plant lines. © 2013 Published by Elsevier Inc.

Diabetes-associated microbiota in fa/fa rats is modified by Roux-en-Y gastric bypass.

PubMed

Arora, Tulika; Seyfried, Florian; Docherty, Neil G; Tremaroli, Valentina; le Roux, Carel W; Perkins, Rosie; Bäckhed, Fredrik

2017-09-01

Roux-en-Y gastric bypass (RYGB) and duodenal jejunal bypass (DJB), two different forms of bariatric surgery, are associated with improved glucose tolerance, but it is not clear whether the gut microbiota contributes to this effect. Here we used fa/fa rats as a model of impaired glucose tolerance to investigate whether (i) the microbiota varies between fa/fa and nondiabetic fa/+ rats; (ii) the microbiota of fa/fa rats is affected by RYGB and/or DJB; and (iii) surgically induced microbiota alterations contribute to glucose metabolism. We observed a profound expansion of Firmicutes (specifically, Lactobacillus animalis and Lactobacillus reuteri) in the small intestine of diabetic fa/fa compared with nondiabetic fa/+ rats. RYGB-, but not DJB-, treated fa/fa rats exhibited greater microbiota diversity in the ileum and lower L. animalis and L. reuteri abundance compared with sham-operated fa/fa rats in all intestinal segments, and their microbiota composition resembled that of unoperated fa/+ rats. To investigate the functional role of RYGB-associated microbiota alterations, we transferred microbiota from sham- and RYGB-treated fa/fa rats to germ-free mice. The metabolic phenotype of RYGB-treated rats was not transferred by the transplant of ileal microbiota. In contrast, postprandial peak glucose levels were lower in mice that received cecal microbiota from RYGB- versus sham-operated rats. Thus, diabetes-associated microbiota alterations in fa/fa rats can be modified by RYGB, and modifications in the cecal microbiota may partially contribute to improved glucose tolerance after RYGB.

[Transgenic rice breeding for abiotic stress tolerance--present and future].

PubMed

Zhao, Feng-Yun; Zhang, Hui

2007-01-01

Environmental stresses and the continuing deterioration of arable land, along with an explosive increase in world population, pose serious threats to global agricultural production and food security. Improving the tolerance of the major crop plants to abiotic stresses has been a main goal in agriculture for a long time. As rice is considered one of the major crops, the development of new cultivars with enhanced abiotic stress-tolerance will undoubtedly have an important effect on global food production. The transgenic approach offers an attractive alternative to conventional techniques for the genetic improvement of rice cultivars. In recent years, an array of stress-related genes has already been transferred to rice to improve its resistance against abiotic stresses. Many transgenic rice plants with enhanced abiotic stress-tolerance have been obtained. This article focuses on the progress in the study of abiotic stress tolerance in transgenic rice breeding.

Exploring traditional aus-type rice for metabolites conferring drought tolerance.

PubMed

Casartelli, Alberto; Riewe, David; Hubberten, Hans Michael; Altmann, Thomas; Hoefgen, Rainer; Heuer, Sigrid

2018-01-25

Traditional varieties and landraces belonging to the aus-type group of rice (Oryza sativa L.) are known to be highly tolerant to environmental stresses, such as drought and heat, and are therefore recognized as a valuable genetic resource for crop improvement. Using two aus-type (Dular, N22) and two drought intolerant irrigated varieties (IR64, IR74) an untargeted metabolomics analysis was conducted to identify drought-responsive metabolites associated with tolerance. The superior drought tolerance of Dular and N22 compared with the irrigated varieties was confirmed by phenotyping plants grown to maturity after imposing severe drought stress in a dry-down treatment. Dular and N22 did not show a significant reduction in grain yield compared to well-watered control plants, whereas the intolerant varieties showed a significant reduction in both, total spikelet number and grain yield. The metabolomics analysis was conducted with shoot and root samples of plants at the tillering stage at the end of the dry-down treatment. The data revealed an overall higher accumulation of N-rich metabolites (amino acids and nucleotide-related metabolites allantoin and uridine) in shoots of the tolerant varieties. In roots, the aus-type varieties were characterised by a higher reduction of metabolites representative of glycolysis and the TCA cycle, such as malate, glyceric acid and glyceric acid-3-phosphate. On the other hand, the oligosaccharide raffinose showed a higher fold increase in both, shoots and roots of the sensitive genotypes. The data further showed that, for certain drought-responsive metabolites, differences between the contrasting rice varieties were already evident under well-watered control conditions. The drought tolerance-related metabolites identified in the aus-type varieties provide a valuable set of protective compounds and an entry point for assessing genetic diversity in the underlying pathways for developing drought tolerant rice and other crops.

+Gz tolerance after 14 days bed rest and the effects of rehydration.

NASA Technical Reports Server (NTRS)

Greenleaf, J. E.; Van Beaumont, W.; Bernauer, E. M.; Haines, R. F.; Sandler, H.; Young, H. L.; Yusken, J. W.

1972-01-01

Measurement of the reduction in centrifugation tolerance after two weeks of bedrest with moderate daily exercise, with an attempt to determine if rehydration improves +Gz tolerance. There were significant reductions in +Gz tolerance during bedrest periods at three acceleration levels. Rehydration resulted in a significant increase in tolerance at 2.1G but it did not restore tolerance to control levels. Rehydration did not affect tolerance at 3.2G and 3.8G.

High-protein diet selectively reduces fat mass and improves glucose tolerance in Western-type diet-induced obese rats

PubMed Central

Stengel, Andreas; Goebel-Stengel, Miriam; Wang, Lixin; Hu, Eugenia; Karasawa, Hiroshi; Pisegna, Joseph R.

2013-01-01

Obesity is an increasing health problem. Because drug treatments are limited, diets remain popular. High-protein diets (HPD) reduce body weight (BW), although the mechanisms are unclear. We investigated physiological mechanisms altered by switching diet induced obesity (DIO) rats from Western-type diet (WTD) to HPD. Male rats were fed standard (SD) or WTD (45% calories from fat). After developing DIO (50% of rats), they were switched to SD (15% calories from protein) or HPD (52% calories from protein) for up to 4 weeks. Food intake (FI), BW, body composition, glucose tolerance, insulin sensitivity, and intestinal hormone plasma levels were monitored. Rats fed WTD showed an increased FI and had a 25% greater BW gain after 9 wk compared with SD (P < 0.05). Diet-induced obese rats switched from WTD to HPD reduced daily FI by 30% on day 1, which lasted to day 9 (−9%) and decreased BW during the 2-wk period compared with SD/SD (P < 0.05). During these 2 wk, WTD/HPD rats lost 72% more fat mass than WTD/SD (P < 0.05), whereas lean mass was unaltered. WTD/HPD rats had lower blood glucose than WTD/SD at 30 min postglucose gavage (P < 0.05). The increase of pancreatic polypeptide and peptide YY during the 2-h dark-phase feeding was higher in WTD/HPD compared with WTD/SD (P < 0.05). These data indicate that HPD reduces BW in WTD rats, which may be related to decreased FI and the selective reduction of fat mass accompanied by improved glucose tolerance, suggesting relevant benefits of HPD in the treatment of obesity. PMID:23883680

Activity and Stability of Dispersed Multi Metallic Pt-based Catalysts for CO Tolerance in Proton Exchange Membrane Fuel Cell Anodes.

PubMed

Hassan, Ayaz; Ticianelli, Edson A

2018-01-01

Studies aiming at improving the activity and stability of dispersed W and Mo containing Pt catalysts for the CO tolerance in proton exchange membrane fuel cell (PEMFC) anodes are revised for the following catalyst systems: (1) a carbon supported PtMo electrocatalyst submitted to heat treatments; (2) Pt and PtMo nanoparticles deposited on carbon-supported molybdenum carbides (Mo2C/C); (3) ternary and quaternary materials formed by PtMoFe/C, PtMoRu/C and PtMoRuFe/C and; (4) Pt nanoparticles supported on tungsten carbide/carbon catalysts and its parallel evaluation with carbon supported PtW catalyst. The heat-treated (600 oC) Pt-Mo/C catalyst showed higher hydrogen oxidation activity in the absence and in the presence of CO and better stability, compared to all other Mo-containing catalysts. PtMoRuFe, PtMoFe, PtMoRu supported on carbon and Pt supported on Mo2C/C exhibited similar CO tolerances but better stability, as compared to as-prepared PtMo supported on carbon. Among the tungsten-based catalysts, tungsten carbide supported Pt catalyst showed reasonable performance and reliable stability in comparison to simple carbon supported PtW catalyst, though an uneven level of catalytic activity towards H2 oxidation in presence of CO is observed for the former as compared to Mo containing catalyst. However, a small dissolution of Mo, Ru, Fe and W from the anodes and their migration toward cathodes during the cell operation is observed. These results indicate that the fuel cell performance and stability has been improved but not yet totally resolved.

Comparable efficacy and safety of 8 weeks treatment with agomelatine 25-50mg or fluoxetine 20-40mg in Asian out-patients with major depressive disorder.

PubMed

Shu, L; Sulaiman, A H; Huang, Y S; Fones Soon Leng, C; Crutel, V Strijckmans; Kim, Y S

2014-04-01

This randomized, double-blind study evaluates the efficacy and tolerability of agomelatine, using fluoxetine as an active comparator, in Asian patients suffering from moderate to severe major depressive disorder (MDD). Patients were randomly assigned to receive either agomelatine (25-50mg/day, n=314) or fluoxetine (20-40mg/day, n=314) during an 8-week treatment period. The main outcome measure was the change in Hamilton Depression Rating Scale 17 items (HAM-D17) scores. Secondary efficacy criteria included scores on Clinical Global Impression Severity of illness (CGI-S) and Improvement of illness (CGI-I), patient sleeping improvement using the self-rating Leeds Sleep Evaluation Questionnaire (LSEQ) and anxiety using the Hamilton Anxiety Rating Scale (HAM-A) scores. Tolerability and safety evaluations were based on emergent adverse events. Agomelatine and fluoxetine exert a comparable antidepressant efficacy in the Asian population. Mean changes over 8 weeks were clinically relevant and similar in both groups (-14.8±7.3 and -15.0±8.1 on HAM-D17 scale in agomelatine and fluoxetine groups, respectively). The between-group difference reached statistical significance on non-inferiority test (p=0.015). Clinically relevant decreases in CGI-S and CGI-I scores were observed over the treatment period in both groups. The two treatments were equally effective on the symptoms of both anxiety and sleep. The good tolerability profile and safety of both doses of agomelatine was confirmed in the Asian population. Agomelatine and fluoxetine are equally effective in the treatment of MDD-associated symptoms in Asian depressed patients. Copyright © 2013 Elsevier B.V. All rights reserved.

Assessment of heat tolerance and production performance of Aardi, Damascus, and their crossbred goats

NASA Astrophysics Data System (ADS)

Samara, Emad Mohammed; Abdoun, Khalid Ahmed; Okab, Aly Bassunny; Al-Badwi, Mohammed Abdo; El-Zarei, Mohamed Fawzy; Al-Seaf, Ali Mohamed; Al-Haidary, Ahmed Abrahim

2016-09-01

The question of whether the adaptability and production performance in goats may be enhanced using a crossbreeding program between bucks of a native and heat-tolerant breed and does of an exotic and dual-purpose breed was approached and examined herein by comparing purebred Aardi and Damascus goats and their crossbred lines (i.e., 1/2 Aardi 1/2 Damascus (½A½D) and 1/4 Aardi 3/4 Damascus (¼A¾D)) reared in a region characterized by dry and hot bioclimatic conditions. Twenty-four male 6-month-old kids randomly segregated into four groups (six replicates/group) were used for the experiment. Climatic, thermo-physiological, biophysiological, metabolic, blood hematological, and biochemical measurements were all determined. The obtained results indicated that such a program was proven to be successful. This conclusion was demonstrated by the findings that crossbred goats (i.e., 1/2A1/2D and 1/4A3/4D) under such bioclimatic conditions were able to show ( P < 0.05) higher heat tolerance capabilities compared to purebred Damascus goats as well as manifested ( P < 0.05) higher production performance compared to the purebred Aardi goats. Accordingly, these evidences could emphasize that the crossbreeding may enable these animals to display a simultaneous improvement of both traits by the possible benefits that could arise from heterosis and breed complementarity. Researches dealing with this aspect may very well improve our understanding of goat's production and welfare under harsh environmental conditions. Future studies should include an economic analysis of traits that have the potential to impact the overall profitability to a vertically coordinated system.

The transdermal formulation of rivastigmine improves caregiver burden and treatment adherence of patients with Alzheimer's disease under daily practice conditions

PubMed Central

Adler, G; Mueller, B; Articus, K

2014-01-01

Background Rivastigmine is the only cholinesterase inhibitor (ChEI) available as transdermal patch. The patch was developed to improve gastrointestinal tolerability and treatment adherence to higher dosages as compared with oral medication. Preferences of patients and caregivers for the patch were reported; however, neither patient compliance nor caregiver burden has yet been measured under routine practice conditions. Methods This was a prospective, multi-centre, observational study in patients with Alzheimer's disease treated with rivastigmine patch in Germany. To compare the transdermal with oral dosage forms, physicians were asked to enrol patients who recently switched from oral to transdermal medication. Beyond effectiveness and tolerability, outcome measures were drug adherence evaluated by the Morisky questionnaire, and caregiver burden, measured as the daily time expenditure for dressing the patient, controlling appearance and administration of medication. Results In total, 1104 outpatients (57.5% female gender; mean age 77 ± 7 years) were enrolled in 220 sites. After 6 months of treatment, 67.5% of patients had an improved Clinical Global Impression and the Mini-Mental State Examination score increased from 19.0 ± 5.1 to 20.0 ± 5.2 (p < 0.001); 84.1% of patients were still on treatment, 64.6% on the target dose of 9.5 mg/day. Compliance and patient satisfaction with therapy continuously increased over the study period and average time savings of caregivers added up to 20 min/day. In general, tolerability was deemed good and there were no unexpected adverse events. Conclusions Transdermal rivastigmine is an effective treatment alternative, which may improve adherence and treatment satisfaction of the patient and relieve the caregiver. Controlled parallel-group trials are warranted. Clinical trials registration: none (observational study). PMID:24588972

The transdermal formulation of rivastigmine improves caregiver burden and treatment adherence of patients with Alzheimer's disease under daily practice conditions.

PubMed

Adler, G; Mueller, B; Articus, K

2014-04-01

Rivastigmine is the only cholinesterase inhibitor (ChEI) available as transdermal patch. The patch was developed to improve gastrointestinal tolerability and treatment adherence to higher dosages as compared with oral medication. Preferences of patients and caregivers for the patch were reported; however, neither patient compliance nor caregiver burden has yet been measured under routine practice conditions. This was a prospective, multi-centre, observational study in patients with Alzheimer's disease treated with rivastigmine patch in Germany. To compare the transdermal with oral dosage forms, physicians were asked to enrol patients who recently switched from oral to transdermal medication. Beyond effectiveness and tolerability, outcome measures were drug adherence evaluated by the Morisky questionnaire, and caregiver burden, measured as the daily time expenditure for dressing the patient, controlling appearance and administration of medication. In total, 1104 outpatients (57.5% female gender; mean age 77 ± 7 years) were enrolled in 220 sites. After 6 months of treatment, 67.5% of patients had an improved Clinical Global Impression and the Mini-Mental State Examination score increased from 19.0 ± 5.1 to 20.0 ± 5.2 (p < 0.001); 84.1% of patients were still on treatment, 64.6% on the target dose of 9.5 mg/day. Compliance and patient satisfaction with therapy continuously increased over the study period and average time savings of caregivers added up to 20 min/day. In general, tolerability was deemed good and there were no unexpected adverse events. Transdermal rivastigmine is an effective treatment alternative, which may improve adherence and treatment satisfaction of the patient and relieve the caregiver. Controlled parallel-group trials are warranted. none (observational study). © 2014 Novartis Pharma GmbH. International Journal of Clinical Practice published by John Wiley & Sons Ltd.

Randomized, controlled trial of rasagiline as an add-on to dopamine agonists in Parkinson's disease.

PubMed

Hauser, Robert A; Silver, Dee; Choudhry, Azhar; Eyal, Eli; Isaacson, Stuart

2014-07-01

Dopamine agonists (DA) are often used as first-line monotherapy for the symptomatic control of Parkinson's disease (PD). However, DA monotherapy typically becomes inadequate within a few years, at which time the DA dosage must be increased or other antiparkinsonian medications added. Adding a monoamine oxidase-B (MAO-B) inhibitor to DA monotherapy might improve symptomatic control while maintaining good safety and tolerability. We conducted an 18-week, randomized, double-blind, placebo-controlled trial of rasagiline 1 mg/d as an add-on to DA therapy (ropinirole ≥ 6 mg/d or pramipexole ≥ 1.0 mg/d) in early PD patients whose conditions were not adequately controlled on their current treatment regimen. The primary efficacy variable was the change in total Unified Parkinson Disease Rating Scale (UPDRS) score (sum of parts I, II, and III) from baseline to week 18, comparing rasagiline and placebo groups. The modified intent-to-treat (ITT) population included 321 subjects whose mean ± SD age was 62.6 ± 9.7, and duration of PD was 2.1 ± 2.1 years. Results demonstrated a significantly greater improvement in total UPDRS scores from baseline to week 18 in the rasagiline group compared with the placebo group (least squares [LS] mean difference ± SE, -2.4 ± 0.95; 95% confidence interval [CI], -4.3, -0.5; P = 0.012). Mean improvement (LS mean ± SE) was -3.6 ± 0.68 in the rasagiline group and -1.2 ± 0.68 in the placebo group. Rasagiline was well tolerated, and the most common adverse events (AEs; rasagiline vs. placebo) were dizziness (7.4% vs. 6.1%), somnolence (6.8% vs. 6.7%), and headache (6.2% vs. 4.3%). Rasagiline 1 mg/d provided statistically significant improvement when added to dopamine agonist therapy and was well tolerated. © 2014 International Parkinson and Movement Disorder Society.

Chromium effects on glucose tolerance and insulin sensitivity in persons at risk for diabetes mellitus.

PubMed

Ali, Ather; Ma, Yingying; Reynolds, Jesse; Wise, John Pierce; Inzucchi, Silvio E; Katz, David L

2011-01-01

To investigate the effects of daily chromium picolinate supplementation on serum measures of glucose tolerance and insulin sensitivity in patients at high risk for type 2 diabetes mellitus. We conducted a randomized, double-blind, placebo-controlled, modified cross-over clinical trial with 6-month sequences of intervention and placebo followed by a 6-month postintervention assessment. Adult patients with impaired fasting glucose, impaired glucose tolerance, or metabolic syndrome were enrolled. Participants received 6-month sequences of chromium picolinate or placebo at 1 of 2 dosages (500 or 1000 mcg daily). Primary outcome measures were change in fasting plasma glucose, 2-hour plasma glucose during oral glucose tolerance testing, fasting and 2-hour insulin, and homeostasis model assessment of insulin resistance (HOMA-IR). Secondary outcomes included anthropometric measures, blood pressure, endothelial function, hemoglobin A1c, lipids, and urinary microalbumin. Fifty-nine participants were enrolled. No changes were seen in glucose level, insulin level, or HOMA-IR (all P>.05) after 6 months of chromium at either dosage level (500 mcg or 1000 mcg daily) when compared with placebo. None of the secondary outcomes improved with either chromium dosage compared with placebo (P>.05). Chromium supplementation does not appear to ameliorate insulin resistance or impaired glucose metabolism in patients at risk for type 2 diabetes and thus is unlikely to attenuate diabetes risk.

Comparative proteomic analysis of differentially expressed proteins in the early milky stage of rice grains during high temperature stress

PubMed Central

Liao, Jiang-Lin; Zhou, Hui-Wen; Huang, Ying-Jin

2014-01-01

Rice yield and quality are adversely affected by high temperatures, and these effects are more pronounced at the ‘milky stage’ of the rice grain ripening phase. Identifying the functional proteins involved in the response of rice to high temperature stress may provide the basis for improving heat tolerance in rice. In the present study, a comparative proteomic analysis of paired, genetically similar heat-tolerant and heat-sensitive rice lines was conducted. Two-dimensional electrophoresis (2-DE) revealed a total of 27 differentially expressed proteins in rice grains, predominantly from the heat-tolerant lines. The protein profiles clearly indicated variations in protein expression between the heat-tolerant and heat-sensitive rice lines. Matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry (MALDI-TOF/TOF MS) analysis revealed that 25 of the 27 differentially displayed proteins were homologous to known functional proteins. These homologous proteins were involved in biosynthesis, energy metabolism, oxidation, heat shock metabolism, and the regulation of transcription. Seventeen of the 25 genes encoding the differentially displayed proteins were mapped to rice chromosomes according to the co-segregating conditions between the simple sequence repeat (SSR) markers and the target genes in recombinant inbred lines (RILs). The proteins identified in the present study provide a basis to elucidate further the molecular mechanisms underlying the adaptation of rice to high temperature stress. PMID:24376254

Realm of Thermoalkaline Lipases in Bioprocess Commodities

PubMed Central

2018-01-01

For decades, microbial lipases are notably used as biocatalysts and efficiently catalyze various processes in many important industries. Biocatalysts are less corrosive to industrial equipment and due to their substrate specificity and regioselectivity they produced less harmful waste which promotes environmental sustainability. At present, thermostable and alkaline tolerant lipases have gained enormous interest as biocatalyst due to their stability and robustness under high temperature and alkaline environment operation. Several characteristics of the thermostable and alkaline tolerant lipases are discussed. Their molecular weight and resistance towards a range of temperature, pH, metal, and surfactants are compared. Their industrial applications in biodiesel, biodetergents, biodegreasing, and other types of bioconversions are also described. This review also discusses the advance of fermentation process for thermostable and alkaline tolerant lipases production focusing on the process development in microorganism selection and strain improvement, culture medium optimization via several optimization techniques (i.e., one-factor-at-a-time, surface response methodology, and artificial neural network), and other fermentation parameters (i.e., inoculums size, temperature, pH, agitation rate, dissolved oxygen tension (DOT), and aeration rate). Two common fermentation techniques for thermostable and alkaline tolerant lipases production which are solid-state and submerged fermentation methods are compared and discussed. Recent optimization approaches using evolutionary algorithms (i.e., Genetic Algorithm, Differential Evolution, and Particle Swarm Optimization) are also highlighted in this article. PMID:29666707

Salt-Stress Response Mechanisms Using de Novo Transcriptome Sequencing of Salt-Tolerant and Sensitive Corchorus spp. Genotypes

PubMed Central

Yang, Zemao; Lu, Ruike; Dai, Zhigang; Yan, An; Tang, Qing; Cheng, Chaohua; Xu, Ying; Yang, Wenting; Su, Jianguang

2017-01-01

High salinity is a major environmental stressor for crops. To understand the regulatory mechanisms underlying salt tolerance, we conducted a comparative transcriptome analysis between salt-tolerant and salt-sensitive jute (Corchorus spp.) genotypes in leaf and root tissues under salt stress and control conditions. In total, 68,961 unigenes were identified. Additionally, 11,100 unigenes (including 385 transcription factors (TFs)) exhibited significant differential expression in salt-tolerant or salt-sensitive genotypes. Numerous common and unique differentially expressed unigenes (DEGs) between the two genotypes were discovered. Fewer DEGs were observed in salt-tolerant jute genotypes whether in root or leaf tissues. These DEGs were involved in various pathways, such as ABA signaling, amino acid metabolism, etc. Among the enriched pathways, plant hormone signal transduction (ko04075) and cysteine/methionine metabolism (ko00270) were the most notable. Eight common DEGs across both tissues and genotypes with similar expression profiles were part of the PYL-ABA-PP2C (pyrabactin resistant-like/regulatory components of ABA receptors-abscisic acid-protein phosphatase 2C). The methionine metabolism pathway was only enriched in salt-tolerant jute root tissue. Twenty-three DEGs were involved in methionine metabolism. Overall, numerous common and unique salt-stress response DEGs and pathways between salt-tolerant and salt-sensitive jute have been discovered, which will provide valuable information regarding salt-stress response mechanisms and help improve salt-resistance molecular breeding in jute. PMID:28927022

Overview of lower length scale model development for accident tolerant fuels regarding U3Si2 fuel and FeCrAl cladding

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Yongfeng

2016-09-01

U3Si2 and FeCrAl have been proposed as fuel and cladding concepts, respectively, for accident tolerance fuels with higher tolerance to accident scenarios compared to UO2. However, a lot of key physics and material properties regarding their in-pile performance are yet to be explored. To accelerate the understanding and reduce the cost of experimental studies, multiscale modeling and simulation are used to develop physics-based materials models to assist engineering scale fuel performance modeling. In this report, the lower-length-scale efforts in method and material model development supported by the Accident Tolerance Fuel (ATF) high-impact-problem (HIP) under the NEAMS program are summarized. Significantmore » progresses have been made regarding interatomic potential, phase field models for phase decomposition and gas bubble formation, and thermal conductivity for U3Si2 fuel, and precipitation in FeCrAl cladding. The accomplishments are very useful by providing atomistic and mesoscale tools, improving the current understanding, and delivering engineering scale models for these two ATF concepts.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Young-Ho; Byun, Thak Sang

Accident-tolerant fuels are expected to have considerably longer coping time to respond to the loss of active cooling under severe accidents and, at the same time, have comparable or improved fuel performance during normal operation. The wear resistance of accident tolerant fuels, therefore, needs to be examined to determine the applicability of these cladding candidates to the current operating PWRs because the most common failure of nuclear fuel claddings is still caused by grid-to-rod fretting during normal operations. In this study, reciprocating sliding wear tests on three kinds of cladding candidates for accident-tolerant fuels have been performed to investigate themore » tribological compatibilities of selfmated cladding candidates and to determine the direct applicability of conventional Zirconium-based alloys as supporting structural materials. The friction coefficients of the cladding candidates are strongly influenced by the test environments and coupled materials. The wear test results under water lubrication conditions indicate that the supporting structural materials for the cladding candidates of accident-tolerant fuels need to be replaced with the same cladding materials instead of using conventional Zirconium-based alloys.« less

Evaluation of a Reverse Gradient Garment for prevention of bed-rest deconditioning

NASA Technical Reports Server (NTRS)

Sandler, H.; Dolkas, D.; Newsom, B.; Webb, P.; Annis, J.; Pace, N.; Grunbaum, B. W.

1983-01-01

A Reverse Gradient Garment (RGG) was used to intermittently induce venous pooling in the extremities of a magnitude similar to that seen in going from a lying to standing position during the course of a 15-d period of horizontal bed rest. Venous pooling failed to improve bed-rest-induced losses in +2.5 Gz and +3.0 Gz centrifugation tolerance or to prevent increased heart-rate responses to lower-body negative pressure (LBNP). Four subjects served as controls, four were treated. Tests during the 7-d recovery period showed fluid/electrolyte and body composition values to have returned to pre-bed-rest levels with continued depression of acceleration tolerance times (56% decreased at +2.5 Gz and 74% decreased at +3.0 Gz compared to pre-bed-rest levels) and exaggerated blood insulin response on glucose tolerance testing (blood insulin for treated group increased 95% at 1 h before bed rest and 465% during recovery). This study demonstrates that the physiologic changes after bed rest persist for significant periods of time. Acceleration tolerance time proved to be a sensitive test for the deconditioning process.

A fixed-dose combination tablet of gemigliptin and metformin sustained release has comparable pharmacodynamic, pharmacokinetic, and tolerability profiles to separate tablets in healthy subjects.

PubMed

Park, Sang-In; Lee, Howard; Oh, Jaeseong; Lim, Kyoung Soo; Jang, In-Jin; Kim, Jeong-Ae; Jung, Jong Hyuk; Yu, Kyung-Sang

2015-01-01

In type 2 diabetes mellitus, fixed-dose combination (FDC) can provide the complementary benefits of correction of multiple pathophysiologic defects such as dysfunctions in glycemic or metabolic control while improving compliance compared with separate tablets taken together. The objective of the study reported here was to compare the pharmacodynamic (PD), pharmacokinetic (PK), and tolerability profiles of gemigliptin and extended-release metformin (metformin XR) between FDC and separate tablets. A randomized, open-label, single-dose, two-way, two-period, crossover study was conducted in 28 healthy male volunteers. Two FDC tablets of gemigliptin/metformin 25/500 mg or separate tablets of gemigliptin (50 mg ×1) and metformin XR (500 mg ×2) were orally administered in each period. Serial blood samples were collected up to 48 hours post-dose to determine dipeptidyl peptidase 4 (DPP-4) activity using spectrophotometric assay and concentrations of gemigliptin and metformin using tandem mass spectrometry. Geometric mean ratios (GMRs) of FDC to separate tablet formulations and their 90% confidence intervals (CIs) were calculated to compare the PD and PK parameters between the two formulations. Tolerability was assessed throughout the study. The plasma DPP-4 activity-time curves of the FDC and the separate tablets almost overlapped, leading to a GMR (90% CI) of the FDC to separate tablets for the plasma DPP-4 activity and its maximum inhibition of 1.00 (0.97-1.04) and 0.92 (0.82-1.05), respectively. Likewise, all of the GMRs (90% CIs) of FDC to separate tablets for the area under the plasma concentration-time curve and maximum plasma concentration of gemigliptin and metformin fell entirely within the conventional bioequivalence range of 0.80-1.25. Both the FDC and separate tablets were well tolerated. The PD, PK, and tolerability profiles of gemigliptin and metformin XR in FDC and separate tablets were found to be comparable. The FDC tablet of gemigliptin and metformin sustained release can be a convenient therapeutic option in patients with type 2 diabetes mellitus requiring a combination approach.

Efficacy and Tolerability of Two Different Kinds of Titration of Paroxetine Hydrocloride Solution: an Observational Study.

PubMed

Ielmini, Marta; Poloni, Nicola; Caselli, Ivano; Bianchi, Lucia; Diurni, Marcello; Vender, Simone; Callegari, Camilla

2018-03-13

Depressive disorders are expected to be the second highest cause of morbidity in the world until few years. Moreover, patients with depression frequently show many side effects and low compliance to therapy. To find a more tolerated and more efficacy therapy is a growing need. This observational study investigates the efficacy, safety and tolerability of paroxetine hydrochloride comparing slow versus standard titration in a population affected by Depressive Disoders (according to DSM 5). 186 outpatients were assessed throught the following scales: Hamilton Depression Rating Scale (HDRS) for depression and World Health Organization Quality of Life Scale Bref for the perceived quality of life (WHOQOL BREF). Treatment-emerged Adverse Events (TEAEs) were recorded throught self-reports. Statystical analysys was performed by GraphPad Prism Version 5.1. The efficacy of paroxetine was confirmed in both titrations by the number of clinical remitters (HDRS ≤ 7 at 12 weeks for 53% of the standard titration group and 58% of the slow titration group), without differences. About safety and tolerability there were more frequent TEAEs among the standard titration group (p < 0.01). Comparing WHOQOL BREF between the two groups at the recruitment and at the twelth week emerged a statistically significant difference (p = 0.003), with highest scores reached in slow titration group. Although the short observation period is an evident limit, this study is consistent to the literature about the efficacy of both titrations of paroxetine to improve depression and shows promising results about the increased tolerability of paroxetine slow titration.

Intragraft Molecular Pathways Associated with Tolerance Induction in Renal Transplantation.

PubMed

Gallon, Lorenzo; Mathew, James M; Bontha, Sai Vineela; Dumur, Catherine I; Dalal, Pranav; Nadimpalli, Lakshmi; Maluf, Daniel G; Shetty, Aneesha A; Ildstad, Suzanne T; Leventhal, Joseph R; Mas, Valeria R

2018-02-01

The modern immunosuppression regimen has greatly improved short-term allograft outcomes but not long-term allograft survival. Complications associated with immunosuppression, specifically nephrotoxicity and infection risk, significantly affect graft and patient survival. Inducing and understanding pathways underlying clinical tolerance after transplantation are, therefore, necessary. We previously showed full donor chimerism and immunosuppression withdrawal in highly mismatched allograft recipients using a bioengineered stem cell product (FCRx). Here, we evaluated the gene expression and microRNA expression profiles in renal biopsy samples from tolerance-induced FCRx recipients, paired donor organs before implant, and subjects under standard immunosuppression (SIS) without rejection and with acute rejection. Unlike allograft samples showing acute rejection, samples from FCRx recipients did not show upregulation of T cell- and B cell-mediated rejection pathways. Gene expression pathways differed slightly between FCRx samples and the paired preimplantation donor organ samples, but most of the functional gene networks overlapped. Notably, compared with SIS samples, FCRx samples showed upregulation of genes involved in pathways, like B cell receptor signaling. Additionally, prediction analysis showed inhibition of proinflammatory regulators and activation of anti-inflammatory pathways in FCRx samples. Furthermore, integrative analyses (microRNA and gene expression profiling from the same biopsy sample) identified the induction of regulators with demonstrated roles in the downregulation of inflammatory pathways and maintenance of tissue homeostasis in tolerance-induced FCRx samples compared with SIS samples. This pilot study highlights the utility of molecular intragraft evaluation of pathways related to FCRx-induced tolerance and the use of integrative analyses for identifying upstream regulators of the affected downstream molecular pathways. Copyright © 2018 by the American Society of Nephrology.

Breast-feeding is associated with reduced postpartum maternal glucose intolerance after gestational diabetes.

PubMed

O'Reilly, M; Avalos, G; Dennedy, M C; O'Sullivan, E P; Dunne, F P

2012-05-01

Gestational diabetes mellitus (GDM) is associated with adverse foetal and maternal outcomes, and identifies women at risk of future Type 2 Diabetes Mellitus (T2DM). Breast-feeding may improve postpartum maternal glucose tolerance. We prospectively examined the prevalence of postpartum dysglycaemia after GDM and examined the effect of lactation on postpartum glucose tolerance. We compared postpartum 75g oral glucose tolerance test (OGTT) results from 300 women with GDM and 220 controls with normal gestational glucose tolerance (NGT). Breast-feeding data was collected at time of OGTT. Postpartum OGTT results were classified as normal [fasting plasma glucose (FPG) < 5.6mmol/l, 2-h < 7.8 mmol/l] and abnormal [impaired fasting glucose (IFG), FPG 5.6-6.9 mmol/l; impaired glucose tolerance (IGT), 2-h glucose 7.8-11 mmol/l; IFG+IGT; T2DM, FPG > or = 7 mmol/l +/- 2h glucose > or = 11.1 mmol/l]. 6 (2.7%) with NGT in pregnancy had postpartum dysglycaemia compared to 57 (19%) with GDM in index pregnancy (p < 0.001). Non-European ethnicity (OR 3.40, 95% CI 1.45-8.02, p = 0.005), family history of T2DM (OR 2.14, 95% CI 1.06-4.32, p = 0.034) and gestational insulin use (OR 2.62, 95% CI 1.17-5.87 p = 0.019) were associated with persistent dysglycaemia. The prevalence of persistent hyperglycaemia was significantly lower in women who breast-fed versus bottle-fed postpartum (8.2% v 18.4%, p < 0.001). Breast-feeding may confer beneficial metabolic effects after GDM and should be encouraged.

Bacillus coagulans tolerance to 1-ethyl-3-methylimidazolium-based ionic liquids in aqueous and solid-state thermophilic culture.

PubMed

Simmons, Christopher W; Reddy, Amitha P; Vandergheynst, Jean S; Simmons, Blake A; Singer, Steven W

2014-01-01

The use of ionic liquids (ILs) to disrupt the recalcitrant structure of lignocellulose and make polysaccharides accessible to hydrolytic enzymes is an emerging technology for biomass pretreatment in lignocellulosic biofuel production. Despite efforts to reclaim and recycle IL from pretreated biomass, residual IL can be inhibitory to microorganisms used for downstream fermentation. As a result, pathways for IL tolerance are needed to improve the activity of fermentative organisms in the presence of IL. In this study, microbial communities from compost were cultured under high-solids and thermophilic conditions in the presence of 1-ethyl-3-methylimidazolium-based ILs to enrich for IL-tolerant microorganisms. A strain of Bacillus coagulans isolated from an IL-tolerant community was grown in liquid and solid-state culture in the presence of the ILs 1-ethyl-3-methylimidazolium acetate ([C2mim][OAc]) or 1-ethyl-3-methylimidazolium chloride ([C2mim][Cl]) to gauge IL tolerance. Viability and respiration varied with the concentration of IL applied and the type of IL used. B. coagulans maintained growth and respiration in the presence of 4 wt% IL, a concentration similar to that present on IL-pretreated biomass. In the presence of both [C2mim][OAc] and [C2mim][Cl] in liquid culture, B. coagulans grew at a rate approximately half that observed in the absence of IL. However, in solid-state culture, the bacteria were significantly more tolerant to [C2mim][Cl] compared with [C2mim][OAc]. B. coagulans tolerance to IL under industrially relevant conditions makes it a promising bacterium for understanding mechanisms of IL tolerance and discovering IL tolerance pathways for use in other microorganisms, particularly those used in bioconversion of IL-pretreated plant biomass. © 2013 American Institute of Chemical Engineers.

Synergistic Effects of Bacillus amyloliquefaciens (GB03) and Water Retaining Agent on Drought Tolerance of Perennial Ryegrass

PubMed Central

Su, An-Yu; Niu, Shu-Qi; Liu, Yuan-Zheng; He, Ao-Lei; Zhao, Qi; Li, Meng-Fei; Han, Qing-Qing; Ali Khan, Sardar

2017-01-01

Water retaining agent (WRA) is widely used for soil erosion control and agricultural water saving. Here, we evaluated the effects of the combination of beneficial soil bacterium Bacillus amyloliquefaciens strain GB03 and WRA (the compound is super absorbent hydrogels) on drought tolerance of perennial ryegrass (Lolium perenne L.). Seedlings were subjected to natural drought for maximum 20 days by stopping watering and then rewatered for seven days. Plant survival rate, biomass, photosynthesis, water status and leaf cell membrane integrity were measured. The results showed that under severe drought stress (20-day natural drought), compared to control, GB03, WRA and GB03+WRA all significantly improved shoot fresh weight, dry weight, relative water content (RWC) and chlorophyll content and decreased leaf relative electric conductivity (REC) and leaf malondialdehyde (MDA) content; GB03+WRA significantly enhanced chlorophyll content compared to control and other two treatments. Seven days after rewatering, GB03, WRA and GB03+WRA all significantly enhanced plant survival rate, biomass, RWC and maintained chlorophyll content compared to control; GB03+WRA significantly enhanced plant survival rate, biomass and chlorophyll content compared to control and other two treatments. The results established that GB03 together with water retaining agent promotes ryegrass growth under drought conditions by improving survival rate and maintaining chlorophyll content. PMID:29232909

Synergistic Effects of Bacillus amyloliquefaciens (GB03) and Water Retaining Agent on Drought Tolerance of Perennial Ryegrass.

PubMed

Su, An-Yu; Niu, Shu-Qi; Liu, Yuan-Zheng; He, Ao-Lei; Zhao, Qi; Paré, Paul W; Li, Meng-Fei; Han, Qing-Qing; Ali Khan, Sardar; Zhang, Jin-Lin

2017-12-11

Water retaining agent (WRA) is widely used for soil erosion control and agricultural water saving. Here, we evaluated the effects of the combination of beneficial soil bacterium Bacillus amyloliquefaciens strain GB03 and WRA (the compound is super absorbent hydrogels) on drought tolerance of perennial ryegrass ( Lolium perenne L.). Seedlings were subjected to natural drought for maximum 20 days by stopping watering and then rewatered for seven days. Plant survival rate, biomass, photosynthesis, water status and leaf cell membrane integrity were measured. The results showed that under severe drought stress (20-day natural drought), compared to control, GB03, WRA and GB03+WRA all significantly improved shoot fresh weight, dry weight, relative water content (RWC) and chlorophyll content and decreased leaf relative electric conductivity (REC) and leaf malondialdehyde (MDA) content; GB03+WRA significantly enhanced chlorophyll content compared to control and other two treatments. Seven days after rewatering, GB03, WRA and GB03+WRA all significantly enhanced plant survival rate, biomass, RWC and maintained chlorophyll content compared to control; GB03+WRA significantly enhanced plant survival rate, biomass and chlorophyll content compared to control and other two treatments. The results established that GB03 together with water retaining agent promotes ryegrass growth under drought conditions by improving survival rate and maintaining chlorophyll content.

Metabolomics-based prediction models of yeast strains for screening of metabolites contributing to ethanol stress tolerance

NASA Astrophysics Data System (ADS)

Hashim, Z.; Fukusaki, E.

2016-06-01

The increased demand for clean, sustainable and renewable energy resources has driven the development of various microbial systems to produce biofuels. One of such systems is the ethanol-producing yeast. Although yeast produces ethanol naturally using its native pathways, production yield is low and requires improvement for commercial biofuel production. Moreover, ethanol is toxic to yeast and thus ethanol tolerance should be improved to further enhance ethanol production. In this study, we employed metabolomics-based strategy using 30 single-gene deleted yeast strains to construct multivariate models for ethanol tolerance and screen metabolites that relate to ethanol sensitivity/tolerance. The information obtained from this study can be used as an input for strain improvement via metabolic engineering.

Impact of CPAP on physical exercise tolerance and sympathetic-vagal balance in patients with chronic heart failure.

PubMed

Reis, Hugo V; Borghi-Silva, Audrey; Catai, Aparecida M; Reis, Michel S

2014-01-01

Chronic heart failure (CHF) leads to exercise intolerance. However, non-invasive ventilation is able to improve functional capacity of patients with CHF. The aim of this study was to evaluate the effectiveness of continuous positive airway pressure (CPAP) on physical exercise tolerance and heart rate variability (HRV) in patients with CHF. Method : Seven men with CHF (62 ± 8 years) and left ventricle ejection fraction of 41 ± 8% were submitted to an incremental symptom-limited exercise test (IT) on the cicloergometer. On separate days, patients were randomized to perform four constant work rate exercise tests to maximal tolerance with and without CPAP (5 cmH2O) in the following conditions: i) at 50% of peak work rate of IT; and ii) at 75% of peak work rate of IT. At rest and during these conditions, instantaneous heart rate (HR) was recorded using a cardiofrequencimeter and HRV was analyzed in time domain (SDNN and RMSSD indexes). For statistical procedures, Wilcoxon test or Kruskall-Wallis test with Dunn's post-hoc were used accordingly. In addition, categorical variables were analysed through Fischer's test (p<0.05). There were significant improvements in exercise tolerance at 75% of peak work rate of IT with CPAP (405 ± 52 vs. 438 ± 58 s). RMSSD indexes were lower during exercise tests compared to CPAP at rest and with 50% of peak work rate of IT. These data suggest that CPAP appears to be a useful strategy to improve functional capacity in patients with CHF. However, the positive impact of CPAP did not generate significant changes in the HRV during physical exercises.

Transcriptional regulation of heat shock proteins and ascorbate peroxidase by CtHsfA2b from African bermudagrass conferring heat tolerance in Arabidopsis

PubMed Central

Wang, Xiuyun; Huang, Wanlu; Yang, Zhimin; Liu, Jun; Huang, Bingru

2016-01-01

Heat stress transcription factor A2s (HsfA2s) are key regulators in plant response to high temperature. Our objectives were to isolate an HsfA2 gene (CtHsfA2b) from a warm-season grass species, African bermudagrass (Cynodon transvaalensis Burtt-Davy), and to determine the physiological functions and transcriptional regulation of HsfA2 for improving heat tolerance. Gene expression analysis revealed that CtHsfA2b was heat-inducible and exhibited rapid response to increasing temperature. Ectopic expression of CtHsfA2b improved heat tolerance in Arabidopsis and restored heat-sensitive defects of Arabidopsis hsfa2 mutant, which was demonstrated by higher survival rate and photosynthetic parameters, and lower electrolyte leakage in transgenic plants compared to the WT or hsfa2 mutant. CtHsfA2b transgenic plants showed elevated transcriptional regulation of several downstream genes, including those encoding ascorbate peroxidase (AtApx2) and heat shock proteins [AtHsp18.1-CI, AtHsp22.0-ER, AtHsp25.3-P and AtHsp26.5-P(r), AtHsp70b and AtHsp101-3]. CtHsfA2b was found to bind to the heat shock element (HSE) on the promoter of AtApx2 and enhanced transcriptional activity of AtApx2. These results suggested that CtHsfA2b could play positive roles in heat protection by up-regulating antioxidant defense and chaperoning mechanisms. CtHsfA2b has the potential to be used as a candidate gene to genetically modify cool-season species for improving heat tolerance. PMID:27320381

Bazedoxifene/conjugated estrogens for managing the burden of estrogen deficiency symptoms.

PubMed

Mirkin, Sebastian; Ryan, Kelly A; Chandran, Arthi B; Komm, Barry S

2014-01-01

The bothersome vasomotor and vaginal symptoms and bone loss that accompany the menopausal transition are associated with significant direct costs due to physician visits and medication, as well as indirect costs from reduced health-related quality of life (HRQoL) and work productivity. With life expectancies increasing, the number of postmenopausal women is also increasing, and more women are remaining in the workforce. These factors have led to an increased burden of menopausal symptoms on healthcare systems. Hormone therapy (HT) has been shown to effectively reduce menopausal symptoms and significantly increase quality-adjusted life years in postmenopausal women, particularly in women experiencing severe symptoms. However, many women discontinue use of HT before their symptoms have dissipated due to safety and tolerability concerns. The tissue selective estrogen complex (TSEC) that pairs bazedoxifene (BZA) with conjugated estrogens (CE) has been developed to provide relief of menopausal symptoms and prevent bone loss without stimulating the breast or endometrium, and to have improved tolerability compared with HT. In this context, BZA 20mg/CE 0.45 and 0.625 mg were shown to prevent bone loss and effectively treat menopausal symptoms in postmenopausal women with an intact uterus, while also demonstrating a favorable safety/tolerability profile. BZA 20mg/CE 0.45 and 0.625 mg were further associated with clinically significant improvements in HRQoL, sleep, and treatment satisfaction. Taken together, the reduction in menopausal symptoms, improvement in HRQoL, and favorable safety/tolerability profile associated with BZA/CE suggest that it is a cost-effective alternative to HT for managing the burden of menopausal symptoms. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Deletion of interleukin 1 receptor-associated kinase 1 (Irak1) improves glucose tolerance primarily by increasing insulin sensitivity in skeletal muscle.

PubMed

Sun, Xiao-Jian; Kim, Soohyun Park; Zhang, Dongming; Sun, Helen; Cao, Qi; Lu, Xin; Ying, Zhekang; Li, Liwu; Henry, Robert R; Ciaraldi, Theodore P; Taylor, Simeon I; Quon, Michael J

2017-07-21

Chronic inflammation may contribute to insulin resistance via molecular cross-talk between pathways for pro-inflammatory and insulin signaling. Interleukin 1 receptor-associated kinase 1 (IRAK-1) mediates pro-inflammatory signaling via IL-1 receptor/Toll-like receptors, which may contribute to insulin resistance, but this hypothesis is untested. Here, we used male Irak1 null (k/o) mice to investigate the metabolic role of IRAK-1. C57BL/6 wild-type (WT) and k/o mice had comparable body weights on low-fat and high-fat diets (LFD and HFD, respectively). After 12 weeks on LFD (but not HFD), k/o mice ( versus WT) had substantially improved glucose tolerance (assessed by the intraperitoneal glucose tolerance test (IPGTT)). As assessed with the hyperinsulinemic euglycemic glucose clamp technique, insulin sensitivity was 30% higher in the Irak1 k/o mice on chow diet, but the Irak1 deletion did not affect IPGTT outcomes in mice on HFD, suggesting that the deletion did not overcome the impact of obesity on glucose tolerance. Moreover, insulin-stimulated glucose-disposal rates were higher in the k/o mice, but we detected no significant difference in hepatic glucose production rates (± insulin infusion). Positron emission/computed tomography scans indicated higher insulin-stimulated glucose uptake in muscle, but not liver, in Irak1 k/o mice in vivo Moreover, insulin-stimulated phosphorylation of Akt was higher in muscle, but not in liver, from Irak1 k/o mice ex vivo In conclusion, Irak1 deletion improved muscle insulin sensitivity, with the effect being most apparent in LFD mice. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Efficacy and tolerability of EPs 7630 in children and adolescents with acute bronchitis - a randomized, double-blind, placebo-controlled multicenter trial with a herbal drug preparation from Pelargonium sidoides roots.

PubMed

Kamin, W; Maydannik, V; Malek, F A; Kieser, M

2010-03-01

The study aim was to demonstrate the efficacy and to investigate the tolerability of EPs 7630, a herbal drug preparation from Pelargonium sidoides roots, in the treatment of patients (1 - 18 years) with acute bronchitis outside the strict indication for antibiotics. A total of 200 patients were randomized to receive either active drug containing EPs 7630 (1 - 6 years: 3 x 10 drops/d; > 6 - 12 years: 3 x 20 drops/d; > 12 - 18 years: 3 x 30 drops/d) or placebo for 7 consecutive days. change in the total score of bronchitis-specific symptoms (BSS) from Day 0 to Day 7. Main secondary outcome measures: treatment outcome, patients' satisfaction with treatment, onset of effect, bed rest. From baseline to Day 7, the mean BSS score improved significantly more for EPs 7630 compared with placebo (3.4 +/- 1.8 vs. 1.2 +/- 1.8 points, p < 0.0001). On Day 7, treatment outcome was significantly better (p < 0.0001), satisfaction with treatment more pronounced (77.6% vs. 25.8%, p < 0.0001), onset of effect faster, and time of bed rest shorter as compared with placebo. Tolerability was similarly good in both groups. All adverse events were assessed as non-serious. EPs 7630 was shown to be efficacious and safe in the treatment of acute bronchitis in children and adolescents outside the strict indication for antibiotics with patients treated with EPs 7630 perceiving a more favorable course of the disease and a good tolerability as compared with placebo.

Introduction of Pea DNA Helicase 45 Into Sugarcane (Saccharum spp. Hybrid) Enhances Cell Membrane Thermostability And Upregulation Of Stress-responsive Genes Leads To Abiotic Stress Tolerance.

PubMed

Augustine, Sruthy Maria; Ashwin Narayan, J; Syamaladevi, Divya P; Appunu, C; Chakravarthi, M; Ravichandran, V; Tuteja, Narendra; Subramonian, N

2015-05-01

DNA helicases are motor proteins that play an essential role in nucleic acid metabolism, by providing a duplex-unwinding function. To improve the drought and salinity tolerance of sugarcane, a DEAD-box helicase gene isolated from pea with a constitutive promoter, Port Ubi 2.3 was transformed into the commercial sugarcane variety Co 86032 through Agrobacterium-mediated transformation, and the transgenics were screened for tolerance to soil moisture stress and salinity. The transgene integration was confirmed through polymerase chain reaction, and the V 0 transgenic events showed significantly higher cell membrane thermostability under normal irrigated conditions. The V 1 transgenic events were screened for tolerance to soil moisture stress and exhibited significantly higher cell membrane thermostability, transgene expression, relative water content, gas exchange parameters, chlorophyll content, and photosynthetic efficiency under soil moisture stress compared to wild-type (WT). The overexpression of PDH45 transgenic sugarcane also led to the upregulation of DREB2-induced downstream stress-related genes. The transgenic events demonstrated higher germination ability and better chlorophyll retention than WT under salinity stress. Our results suggest the possibility for development of increased abiotic stress tolerant sugarcane cultivars through overexpression of PDH45 gene. Perhaps this is the first report, which provides evidence for increased drought and salinity tolerance in sugarcane through overexpression of PDH45.

Screening of Purslane (Portulaca oleracea L.) Accessions for High Salt Tolerance

PubMed Central

Juraimi, Abdul Shukor; Rafii, M. Y.; Abdul Hamid, Azizah

2014-01-01

Purslane (Portulaca oleracea L.) is an herbaceous leafy vegetable crop, comparatively more salt-tolerant than any other vegetables with high antioxidants, minerals, and vitamins. Salt-tolerant crop variety development is of importance due to inadequate cultivable land and escalating salinity together with population pressure. In this view a total of 25 purslane accessions were initially selected from 45 collected purslane accessions based on better growth performance and subjected to 5 different salinity levels, that is, 0.0, 10.0, 20.0, 30.0, and 40.0 dS m−1 NaCl. Plant height, number of leaves, number of flowers, and dry matter contents in salt treated purslane accessions were significantly reduced (P ≤ 0.05) and the enormity of reduction increased with increasing salinity stress. Based on dry matter yield reduction, among all 25 purslane accessions 2 accessions were graded as tolerant (Ac7 and Ac9), 6 accessions were moderately tolerant (Ac3, Ac5, Ac6, Ac10, Ac11, and Ac12), 5 accessions were moderately susceptible (Ac1, Ac2, Ac4, Ac8, and Ac13), and the remaining 12 accessions were susceptible to salinity stress and discarded from further study. The selected 13 purslane accessions could assist in the identification of superior genes for salt tolerance in purslane for improving its productivity and sustainable agricultural production. PMID:25003141

Estimating heat tolerance of plants by ion leakage: a new method based on gradual heating.

PubMed

Ilík, Petr; Špundová, Martina; Šicner, Michal; Melkovičová, Helena; Kučerová, Zuzana; Krchňák, Pavel; Fürst, Tomáš; Večeřová, Kristýna; Panzarová, Klára; Benediktyová, Zuzana; Trtílek, Martin

2018-05-01

Heat tolerance of plants related to cell membrane thermostability is commonly estimated via the measurement of ion leakage from plant segments after defined heat treatment. To compare heat tolerance of various plants, it is crucial to select suitable heating conditions. This selection is time-consuming and optimizing the conditions for all investigated plants may even be impossible. Another problem of the method is its tendency to overestimate basal heat tolerance. Here we present an improved ion leakage method, which does not suffer from these drawbacks. It is based on gradual heating of plant segments in a water bath or algal suspensions from room temperature up to 70-75°C. The electrical conductivity of the bath/suspension, which is measured continuously during heating, abruptly increases at a certain temperature T COND (within 55-70°C). The T COND value can be taken as a measure of cell membrane thermostability, representing the heat tolerance of plants/organisms. Higher T COND corresponds to higher heat tolerance (basal or acquired) connected to higher thermostability of the cell membrane, as evidenced by the common ion leakage method. The new method also enables determination of the thermostability of photochemical reactions in photosynthetic samples via the simultaneous measurement of Chl fluorescence. © 2018 The Authors. New Phytologist © 2018 New Phytologist Trust.

The determinants of leaf turgor loss point and prediction of drought tolerance of species and biomes: a global meta-analysis.

PubMed

Bartlett, Megan K; Scoffoni, Christine; Sack, Lawren

2012-05-01

Increasing drought is one of the most critical challenges facing species and ecosystems worldwide, and improved theory and practices are needed for quantification of species tolerances. Leaf water potential at turgor loss, or wilting (π(tlp) ), is classically recognised as a major physiological determinant of plant water stress response. However, the cellular basis of π(tlp) and its importance for predicting ecological drought tolerance have been controversial. A meta-analysis of 317 species from 72 studies showed that π(tlp) was strongly correlated with water availability within and across biomes, indicating power for anticipating drought responses. We derived new equations giving both π(tlp) and relative water content at turgor loss point (RWC(tlp) ) as explicit functions of osmotic potential at full turgor (π(o) ) and bulk modulus of elasticity (ε). Sensitivity analyses and meta-analyses showed that π(o) is the major driver of π(tlp) . In contrast, ε plays no direct role in driving drought tolerance within or across species, but sclerophylly and elastic adjustments act to maintain RWC(tlp,) preventing cell dehydration, and additionally protect against nutrient, mechanical and herbivory stresses independent of drought tolerance. These findings clarify biogeographic trends and the underlying basis of drought tolerance parameters with applications in comparative assessments of species and ecosystems worldwide. © 2012 Blackwell Publishing Ltd/CNRS.

The tolerance of the human body to automobile collision impact - a systematic review of injury biomechanics research, 1990-2009.

PubMed

Forman, Jason L; Lopez-Valdes, Francisco J; Duprey, Sonia; Bose, Dipan; Del Pozo de Dios, Eduardo; Subit, Damien; Gillispie, Tim; Crandall, Jeff R; Segui-Gomez, Maria

2015-07-01

Road traffic injuries account for 1.3 million deaths per year world-wide. Mitigating both fatalities and injuries requires a detailed understanding of the tolerance of the human body to external load. To identify research priorities, it is necessary to periodically compare trends in injury tolerance research to the characteristics of injuries occurring in the field. This study sought to perform a systematic review on the last twenty years of experimental injury tolerance research, and to evaluate those results relative to available epidemiologic data. Four hundred and eight experimental injury tolerance studies from 1990-2009 were identified from a reference index of over 68,000 papers. Examined variables included the body regions, ages, and genders studied; and the experimental models used. Most (20%) of the publications studied injury to the spine. There has also been a substantial volume of biomechanical research focused on upper and lower extremity injury, thoracic injury, and injury to the elderly - although these injury types still occur with regularity in the field. In contrast, information on pediatric injury and physiological injury (especially in the central nervous system) remains lacking. Given their frequency of injury in the field, future efforts should also include improving our understanding of tolerances and protection of vulnerable road users (e.g., motorcyclists, pedestrians). Copyright © 2015 Elsevier Ltd. All rights reserved.

Four Reasons to Question the Accuracy of a Biotic Index; the Risk of Metric Bias and the Scope to Improve Accuracy

PubMed Central

Monaghan, Kieran A.

2016-01-01

Natural ecological variability and analytical design can bias the derived value of a biotic index through the variable influence of indicator body-size, abundance, richness, and ascribed tolerance scores. Descriptive statistics highlight this risk for 26 aquatic indicator systems; detailed analysis is provided for contrasting weighted-average indices applying the example of the BMWP, which has the best supporting data. Differences in body size between taxa from respective tolerance classes is a common feature of indicator systems; in some it represents a trend ranging from comparatively small pollution tolerant to larger intolerant organisms. Under this scenario, the propensity to collect a greater proportion of smaller organisms is associated with negative bias however, positive bias may occur when equipment (e.g. mesh-size) selectively samples larger organisms. Biotic indices are often derived from systems where indicator taxa are unevenly distributed along the gradient of tolerance classes. Such skews in indicator richness can distort index values in the direction of taxonomically rich indicator classes with the subsequent degree of bias related to the treatment of abundance data. The misclassification of indicator taxa causes bias that varies with the magnitude of the misclassification, the relative abundance of misclassified taxa and the treatment of abundance data. These artifacts of assessment design can compromise the ability to monitor biological quality. The statistical treatment of abundance data and the manipulation of indicator assignment and class richness can be used to improve index accuracy. While advances in methods of data collection (i.e. DNA barcoding) may facilitate improvement, the scope to reduce systematic bias is ultimately limited to a strategy of optimal compromise. The shortfall in accuracy must be addressed by statistical pragmatism. At any particular site, the net bias is a probabilistic function of the sample data, resulting in an error variance around an average deviation. Following standardized protocols and assigning precise reference conditions, the error variance of their comparative ratio (test-site:reference) can be measured and used to estimate the accuracy of the resultant assessment. PMID:27392036

Supervisor tolerance-responsiveness to substance abuse and workplace prevention training: use of a cognitive mapping tool.

PubMed

Bennett, Joel B; Lehman, Wayne E K

2002-02-01

Supervisor tolerance-responsiveness, referring to the attitudes and behaviors associated with either ignoring or taking proactive steps with troubled employees, was investigated in two studies. The studies were conducted to help examine, understand and improve supervisor responsiveness to employee substance abuse. Study 1 examined supervisor response to and tolerance of coworker substance use and ways of interfacing with the Employee Assistance Program (EAP) in two workplaces (n = 244 and 107). These surveys suggested that engaging supervisors in a dialogue about tolerance might improve their willingness to use the EAP. Study 2 was a randomized control field experiment that assessed a team-oriented training. This training adopted a cognitive mapping technique to help improve supervisor responsiveness. Supervisors receiving this training (n = 29) were more likely to improve on several dimensions of responsiveness (e.g. likely to contact the EAP) than were supervisors who received a more didactic, informational training (n = 23) or a no-training control group (n = 17). Trained supervisors also showed increases in their own help-seeking behavior. Procedures and maps from the mapping activity (two-stage conversational mapping) are described. Overall, results indicate that while supervisor tolerance of coworker substance use inhibits EAP utilization, it may be possible to address this tolerance using team-oriented prevention training in the work-site.

Can we well assess the relative efficacy and tolerability of a new drug versus others at the time of marketing authorization using mixed treatment comparisons? A detailed illustration with escitalopram

PubMed Central

Llorca, Pierre-Michel; Lançon, Christophe; Brignone, Mélanie; Painchault, Caroline; Rive, Benoit; Toumi, Mondher; François, Clément

2015-01-01

Objective To assess the variation of relative efficacy and tolerability of an antidepressant versus others based on both pre-marketing (registration studies) and post-marketing studies versus pre-marketing studies only in patients with major depressive disorder. Methods The relative efficacy and tolerability of antidepressants was assessed by mixed treatment comparisons (MTCs) using data acquired over two time periods: before registration of the reference drug escitalopram (1989–2002) and up to 5 years later (1989–2007). Ranking probability outputs were presented for efficacy, using change from baseline to 8 weeks on Montgomery–Åsberg Depression Rating Scale total score, and tolerability, using withdrawals due to adverse events. Results The relative efficacy and tolerability of some selected antidepressants, including escitalopram, varied considerably over the two time periods. The improved relative efficacy and tolerability of escitalopram over time, compared with citalopram, was demonstrated by greater separation of ranking probability curves for efficacy and tolerability. In 2002, escitalopram ranked low with 13.9% and 5.1% probability of being in the top four antidepressants’ relative efficacy and tolerability, respectively. In 2007, ranking probabilities for relative efficacy and tolerability of escitalopram increased to 52.5% and 82.1%, respectively. Conclusions Time of marketing authorization may not be the most appropriate time to evaluate the relative efficacy and tolerability of a new antidepressant based on MTC approach due to the asymmetry of information between new and older compounds. However, the first evaluation of relative effect of a new drug for health technology assessment recommendations is commonly done at this time. Re-evaluation of a drug several years after its launch is likely to provide a more accurate indication of its relative efficacy and tolerability. PMID:27123184

A mild pulsed electric field condition that improves acid tolerance, growth, and protease activity of Lactobacillus acidophilus LA-K and Lactobacillus delbrueckii subspecies bulgaricus LB-12.

PubMed

Najim, N; Aryana, Kayanush J

2013-06-01

Pulsed electric field (PEF) processing involves the application of pulses of voltage for less than 1 s to fluid products placed between 2 electrodes. The effect of mild PEF on beneficial characteristics of probiotic bacteria Lactobacillus acidophilus and Lactobacillus delbrueckii ssp. bulgaricus is not clearly understood. The objective of this study was to determine the influence of mild PEF conditions on acid tolerance, growth, and protease activity of Lb. acidophilus LA-K and Lactobacillus delbrueckii ssp. bulgaricus LB-12. A pilot plant PEF system (OSU-4M; The Ohio State University, Columbus) was used. The PEF treatments were positive square unipolar pulse width of 3 µs, pulse period of 0.5s, electric field strength of 1 kV/cm, delay time of 20 µs, flow rate of 60 mL/min, and 40.5°C PEF treatment temperature. Both Lb. acidophilus LA-K and Lb. bulgaricus LB-12 subjected to mild PEF conditions were acid tolerant until the end of the 120 min of incubation, unlike the Lb. bulgaricus control, which was not acid tolerant after 30 min. The mild PEF-treated Lb. acidophilus LA-K and Lb. bulgaricus LB-12 reached the logarithmic phase of growth an hour earlier than the control. Mild PEF conditions studied significantly improved acid tolerance, exponential growth, and protease activity of both Lb. acidophilus LA-K and Lb. bulgaricus LB-12 compared with the control. The mild PEF conditions studied can be recommended for pretreating cultures to enhance these desirable attributes. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

IMPROVEMENT OF SMVGEAR II ON VECTOR AND SCALAR MACHINES THROUGH ABSOLUTE ERROR TOLERANCE CONTROL (R823186)

EPA Science Inventory

The computer speed of SMVGEAR II was improved markedly on scalar and vector machines with relatively little loss in accuracy. The improvement was due to a method of frequently recalculating the absolute error tolerance instead of keeping it constant for a given set of chemistry. ...

Houttuynia cordata Facilitates Metformin on Ameliorating Insulin Resistance Associated with Gut Microbiota Alteration in OLETF Rats.

PubMed

Wang, Jing-Hua; Bose, Shambhunath; Lim, Soo-Kyoung; Ansari, AbuZar; Chin, Young-Won; Choi, Han Seok; Kim, Hojun

2017-09-22

Metformin and Houttuynia cordata are representative anti-diabetic therapeutics in western and oriental medicine, respectively. The current study examined the synergistic anti-diabetic effect of Houttuynia cordata extraction (HCE) and metformin combination in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Fecal microbiota were analyzed by denaturing gradient gel electrophoresis (DGGE) and real-time PCR. Combining HCE + metformin resulted in significantly ameliorated glucose tolerance (oral glucose tolerance test (OGTT))-the same as metformin alone. Particularly, results of the insulin tolerance test (ITT) showed that combining HCE + metformin dramatically improved insulin sensitivity as compared to metformin treatment alone. Both fecal and serum endotoxin, as well as cytokines (tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6)) were significantly ameliorated by HCE + metformin compared to metformin alone. Meanwhile, the activation of AMPK (adenosine monophosphate-activated protein kinase) by metformin was distinctly enhanced by HCE. Both of HCE and metformin evidently changed the gut microbiota composition, causing the alteration of bacterial metabolite, like short-chain fatty acids. H. cordata , together with metformin, exerts intensive sensibilization to insulin; the corresponding mechanisms are associated with alleviation of endotoxemia via regulation of gut microbiota, particularly Roseburia , Akkermansia , and Gram-negative bacterium.

Houttuynia cordata Facilitates Metformin on Ameliorating Insulin Resistance Associated with Gut Microbiota Alteration in OLETF Rats

PubMed Central

Bose, Shambhunath; Lim, Soo-Kyoung; Ansari, AbuZar; Chin, Young-Won; Choi, Han Seok; Kim, Hojun

2017-01-01

Metformin and Houttuynia cordata are representative anti-diabetic therapeutics in western and oriental medicine, respectively. The current study examined the synergistic anti-diabetic effect of Houttuynia cordata extraction (HCE) and metformin combination in Otsuka Long–Evans Tokushima Fatty (OLETF) rats. Fecal microbiota were analyzed by denaturing gradient gel electrophoresis (DGGE) and real-time PCR. Combining HCE + metformin resulted in significantly ameliorated glucose tolerance (oral glucose tolerance test (OGTT))—the same as metformin alone. Particularly, results of the insulin tolerance test (ITT) showed that combining HCE + metformin dramatically improved insulin sensitivity as compared to metformin treatment alone. Both fecal and serum endotoxin, as well as cytokines (tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6)) were significantly ameliorated by HCE + metformin compared to metformin alone. Meanwhile, the activation of AMPK (adenosine monophosphate-activated protein kinase) by metformin was distinctly enhanced by HCE. Both of HCE and metformin evidently changed the gut microbiota composition, causing the alteration of bacterial metabolite, like short-chain fatty acids. H. cordata, together with metformin, exerts intensive sensibilization to insulin; the corresponding mechanisms are associated with alleviation of endotoxemia via regulation of gut microbiota, particularly Roseburia, Akkermansia, and Gram-negative bacterium. PMID:28937612

High Performance and Cost-Effective Direct Methanol Fuel Cells: Fe-N-C Methanol-Tolerant Oxygen Reduction Reaction Catalysts.

PubMed

Sebastián, David; Serov, Alexey; Artyushkova, Kateryna; Gordon, Jonathan; Atanassov, Plamen; Aricò, Antonino S; Baglio, Vincenzo

2016-08-09

Direct methanol fuel cells (DMFCs) offer great advantages for the supply of power with high efficiency and large energy density. The search for a cost-effective, active, stable and methanol-tolerant catalyst for the oxygen reduction reaction (ORR) is still a great challenge. In this work, platinum group metal-free (PGM-free) catalysts based on Fe-N-C are investigated in acidic medium. Post-treatment of the catalyst improves the ORR activity compared with previously published PGM-free formulations and shows an excellent tolerance to the presence of methanol. The feasibility for application in DMFC under a wide range of operating conditions is demonstrated, with a maximum power density of approximately 50 mW cm(-2) and a negligible methanol crossover effect on the performance. A review of the most recent PGM-free cathode formulations for DMFC indicates that this formulation leads to the highest performance at a low membrane-electrode assembly (MEA) cost. Moreover, a 100 h durability test in DMFC shows suitable applicability, with a similar performance-time behavior compared to common MEAs based on Pt cathodes. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Metabolomic approach for improving ethanol stress tolerance in Saccharomyces cerevisiae.

PubMed

Ohta, Erika; Nakayama, Yasumune; Mukai, Yukio; Bamba, Takeshi; Fukusaki, Eiichiro

2016-04-01

The budding yeast Saccharomyces cerevisiae is widely used for brewing and ethanol production. The ethanol sensitivity of yeast cells is still a serious problem during ethanol fermentation, and a variety of genetic approaches (e.g., random mutant screening under selective pressure of ethanol) have been developed to improve ethanol tolerance. In this study, we developed a strategy for improving ethanol tolerance of yeast cells based on metabolomics as a high-resolution quantitative phenotypic analysis. We performed gas chromatography-mass spectrometry analysis to identify and quantify 36 compounds on 14 mutant strains including knockout strains for transcription factor and metabolic enzyme genes. A strong relation between metabolome of these mutants and their ethanol tolerance was observed. Data mining of the metabolomic analysis showed that several compounds (such as trehalose, valine, inositol and proline) contributed highly to ethanol tolerance. Our approach successfully detected well-known ethanol stress related metabolites such as trehalose and proline thus, to further prove our strategy, we focused on valine and inositol as the most promising target metabolites in our study. Our results show that simultaneous deletion of LEU4 and LEU9 (leading to accumulation of valine) or INM1 and INM2 (leading to reduction of inositol) significantly enhanced ethanol tolerance. This study shows the potential of the metabolomic approach to identify target genes for strain improvement of S. cerevisiae with higher ethanol tolerance. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Characterization and Regulation of Aquaporin Genes of Sorghum [Sorghum bicolor (L.) Moench] in Response to Waterlogging Stress

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kadam, Suhas; Abril, Alejandra; Dhanapal, Arun P.

Waterlogging is a significant environmental constraint to crop production, and a better understanding of plant responses is critical for the improvement of crop tolerance to waterlogged soils. Aquaporins (AQPs) are a class of channel-forming proteins that play an important role in water transport in plants. Our study aimed to examine the regulation of AQP genes under waterlogging stress and to characterize the genetic variability of AQP genes in sorghum (Sorghum bicolor). Transcriptional profiling of AQP genes in response to waterlogging stress in nodal root tips and nodal root basal regions of two tolerant and two sensitive sorghum genotypes at 18more » and 96 h after waterlogging stress imposition revealed significant gene-specific pattern with regard to genotype, root tissue sample, and time point. For some tissue sample and time point combinations, PIP2-6, PIP2-7, TIP2-2, TIP4-4, and TIP5-1 expression was differentially regulated in tolerant compared to sensitive genotypes. The differential response of these AQP genes suggests that they may play a tissue specific role in mitigating waterlogging stress. Genetic analysis of sorghum revealed that AQP genes were clustered into the same four subfamilies as in maize (Zea mays) and rice (Oryza sativa) and that residues determining the AQP channel specificity were largely conserved across species. Single nucleotide polymorphism (SNP) data from 50 sorghum accessions were used to build an AQP gene-based phylogeny of the haplotypes. Phylogenetic analysis based on single nucleotide polymorphisms of sorghum AQP genes placed the tolerant and sensitive genotypes used for the expression study in distinct groups. Expression analyses suggested that selected AQPs may play a pivotal role in sorghum tolerance to water logging stress. Furthermore experimentation is needed to verify their role and to leverage phylogenetic analyses and AQP expression data to improve water logging tolerance in sorghum.« less

Characterization and Regulation of Aquaporin Genes of Sorghum [Sorghum bicolor (L.) Moench] in Response to Waterlogging Stress

DOE PAGES

Kadam, Suhas; Abril, Alejandra; Dhanapal, Arun P.; ...

2017-05-30

Waterlogging is a significant environmental constraint to crop production, and a better understanding of plant responses is critical for the improvement of crop tolerance to waterlogged soils. Aquaporins (AQPs) are a class of channel-forming proteins that play an important role in water transport in plants. Our study aimed to examine the regulation of AQP genes under waterlogging stress and to characterize the genetic variability of AQP genes in sorghum (Sorghum bicolor). Transcriptional profiling of AQP genes in response to waterlogging stress in nodal root tips and nodal root basal regions of two tolerant and two sensitive sorghum genotypes at 18more » and 96 h after waterlogging stress imposition revealed significant gene-specific pattern with regard to genotype, root tissue sample, and time point. For some tissue sample and time point combinations, PIP2-6, PIP2-7, TIP2-2, TIP4-4, and TIP5-1 expression was differentially regulated in tolerant compared to sensitive genotypes. The differential response of these AQP genes suggests that they may play a tissue specific role in mitigating waterlogging stress. Genetic analysis of sorghum revealed that AQP genes were clustered into the same four subfamilies as in maize (Zea mays) and rice (Oryza sativa) and that residues determining the AQP channel specificity were largely conserved across species. Single nucleotide polymorphism (SNP) data from 50 sorghum accessions were used to build an AQP gene-based phylogeny of the haplotypes. Phylogenetic analysis based on single nucleotide polymorphisms of sorghum AQP genes placed the tolerant and sensitive genotypes used for the expression study in distinct groups. Expression analyses suggested that selected AQPs may play a pivotal role in sorghum tolerance to water logging stress. Furthermore experimentation is needed to verify their role and to leverage phylogenetic analyses and AQP expression data to improve water logging tolerance in sorghum.« less

Some Biological Hints on the Control of Heat and Mass Transfer

NASA Astrophysics Data System (ADS)

Hagiwara, Yoshimichi

This review paper explores the possibilities of the control of heat and mass transfer associated with drought tolerance and freeze tolerance. The accumulation of some metabolites, such as proline and trehalose, are effective for drought tolerance. The special microstructures on the surfaces of some plants and insects in deserts are effective for collecting moisture in the air. Methods of preserving crops will be improved by the mimetic of the drought tolerance. Calcium ions and a protein are effective for the retrieval of damaged cell membrane due to ice formation. Ice crystal growth is inhibited by some substances such as antifreeze proteins. The cryopreservation of foods and organs will be improved by the mimetic of the freeze tolerance.

Transgenic rice expressing a codon-modified synthetic CP4-EPSPS confers tolerance to broad-spectrum herbicide, glyphosate.

PubMed

Chhapekar, Sushil; Raghavendrarao, Sanagala; Pavan, Gadamchetty; Ramakrishna, Chopperla; Singh, Vivek Kumar; Phanindra, Mullapudi Lakshmi Venkata; Dhandapani, Gurusamy; Sreevathsa, Rohini; Ananda Kumar, Polumetla

2015-05-01

Highly tolerant herbicide-resistant transgenic rice was developed by expressing codon-modified synthetic CP4--EPSPS. The transformants could tolerate up to 1% commercial glyphosate and has the potential to be used for DSR (direct-seeded rice). Weed infestation is one of the major biotic stress factors that is responsible for yield loss in direct-seeded rice (DSR). Herbicide-resistant rice has potential to improve the efficiency of weed management under DSR. Hence, the popular indica rice cultivar IR64, was genetically modified using Agrobacterium-mediated transformation with a codon-optimized CP4-EPSPS (5-enolpyruvylshikimate-3-phosphate synthase) gene, with N-terminal chloroplast targeting peptide from Petunia hybrida. Integration of the transgenes in the selected rice plants was confirmed by Southern hybridization and expression by Northern and herbicide tolerance assays. Transgenic plants showed EPSPS enzyme activity even at high concentrations of glyphosate, compared to untransformed control plants. T0, T1 and T2 lines were tested by herbicide bioassay and it was confirmed that the transgenic rice could tolerate up to 1% of commercial Roundup, which is five times more in dose used to kill weeds under field condition. All together, the transgenic rice plants developed in the present study could be used efficiently to overcome weed menace.

Comparison of phenotypic methods and matrix-assisted laser desorption ionisation time-of-flight mass spectrometry for the identification of aero-tolerant Actinomyces spp. isolated from soft-tissue infections.

PubMed

Ng, L S Y; Sim, J H C; Eng, L C; Menon, S; Tan, T Y

2012-08-01

Aero-tolerant Actinomyces spp. are an under-recognised cause of cutaneous infections, in part because identification using conventional phenotypic methods is difficult and may be inaccurate. Matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS) is a promising new technique for bacterial identification, but with limited data on the identification of aero-tolerant Actinomyces spp. This study evaluated the accuracy of a phenotypic biochemical kit, MALDI-TOF MS and genotypic identification methods for the identification of this problematic group of organisms. Thirty aero-tolerant Actinomyces spp. were isolated from soft-tissue infections over a 2-year period. Species identification was performed by 16 s rRNA sequencing and genotypic results were compared with results obtained by API Coryne and MALDI-TOF MS. There was poor agreement between API Coryne and genotypic identification, with only 33% of isolates correctly identified to the species level. MALDI-TOF MS correctly identified 97% of isolates to the species level, with 33% of identifications achieved with high confidence scores. MALDI-TOF MS is a promising new tool for the identification of aero-tolerant Actinomyces spp., but improvement of the database is required in order to increase the confidence level of identification.

Comparison of Leaf Sheath Transcriptome Profiles with Physiological Traits of Bread Wheat Cultivars under Salinity Stress

PubMed Central

Trittermann, Christine; Berger, Bettina; Roy, Stuart J.; Seki, Motoaki; Shinozaki, Kazuo; Tester, Mark

2015-01-01

Salinity stress has significant negative effects on plant biomass production and crop yield. Salinity tolerance is controlled by complex systems of gene expression and ion transport. The relationship between specific features of mild salinity stress adaptation and gene expression was analyzed using four commercial varieties of bread wheat (Triticum aestivum) that have different levels of salinity tolerance. The high-throughput phenotyping system in The Plant Accelerator at the Australian Plant Phenomics Facility revealed variation in shoot relative growth rate and salinity tolerance among the four cultivars. Comparative analysis of gene expression in the leaf sheaths identified genes whose functions are potentially linked to shoot biomass development and salinity tolerance. Early responses to mild salinity stress through changes in gene expression have an influence on the acquisition of stress tolerance and improvement in biomass accumulation during the early “osmotic” phase of salinity stress. In addition, results revealed transcript profiles for the wheat cultivars that were different from those of usual stress-inducible genes, but were related to those of plant growth. These findings suggest that, in the process of breeding, selection of specific traits with various salinity stress-inducible genes in commercial bread wheat has led to adaptation to mild salinity conditions. PMID:26244554

Overexpression of VP, a vacuolar H+-pyrophosphatase gene in wheat (Triticum aestivum L.), improves tobacco plant growth under Pi and N deprivation, high salinity, and drought.

PubMed

Li, Xiaojuan; Guo, Chengjin; Gu, Juntao; Duan, Weiwei; Zhao, Miao; Ma, Chunying; Du, Xiaoming; Lu, Wenjing; Xiao, Kai

2014-02-01

Establishing crop cultivars with strong tolerance to P and N deprivation, high salinity, and drought is an effective way to improve crop yield and promote sustainable agriculture worldwide. A vacuolar H+-pyrophosphatase (V-H+-PPase) gene in wheat (TaVP) was functionally characterized in this study. TaVP cDNA is 2586-bp long and encodes a 775-amino-acid polypeptide that contains 10 conserved membrane-spanning domains. Transcription of TaVP was upregulated by inorganic phosphate (Pi) and N deprivation, high salinity, and drought. Transgene analysis revealed that TaVP overexpression improved plant growth under normal conditions and specifically under Pi and N deprivation stresses, high salinity, and drought. The improvement of growth of the transgenic plants was found to be closely related to elevated V-H+-PPase activities in their tonoplasts and enlarged root systems, which possibly resulted from elevated expression of auxin transport-associated genes. TaVP-overexpressing plants showed high dry mass, photosynthetic efficiencies, antioxidant enzyme activities, and P, N, and soluble carbohydrate concentrations under various growth conditions, particularly under the stress conditions. The transcription of phosphate and nitrate transporter genes was not altered in TaVP-overexpressing plants compared with the wild type, suggesting that high P and N concentrations regulated by TaVP were caused by increased root absorption area instead of alteration of Pi and NO3- acquisition kinetics. TaVP is important in the tolerance of multiple stresses and can serve as a useful genetic resource to improve plant P- and N-use efficiencies and to increase tolerance to high salinity and drought.

Potential Application of the Oryza sativa Monodehydroascorbate Reductase Gene (OsMDHAR) to Improve the Stress Tolerance and Fermentative Capacity of Saccharomyces cerevisiae

PubMed Central

Kim, Yul-Ho; Park, Ae-Kyung; Kim, Han-Woo; Lee, Jun-Hyuk; Yoon, Ho-Sung

2016-01-01

Monodehydroascorbate reductase (MDHAR; EC 1.6.5.4) is an important enzyme for ascorbate recycling. To examine whether heterologous expression of MDHAR from Oryza sativa (OsMDHAR) can prevent the deleterious effects of unfavorable growth conditions, we constructed a transgenic yeast strain harboring a recombinant plasmid carrying OsMDHAR (p426GPD::OsMDHAR). OsMDHAR-expressing yeast cells displayed enhanced tolerance to hydrogen peroxide by maintaining redox homoeostasis, proteostasis, and the ascorbate (AsA)-like pool following the accumulation of antioxidant enzymes and molecules, metabolic enzymes, and molecular chaperones and their cofactors, compared to wild-type (WT) cells carrying vector alone. The addition of exogenous AsA or its analogue isoascorbic acid increased the viability of WT and ara2Δ cells under oxidative stress. Furthermore, the survival of OsMDHAR-expressing cells was greater than that of WT cells when cells at mid-log growth phase were exposed to high concentrations of ethanol. High OsMDHAR expression also improved the fermentative capacity of the yeast during glucose-based batch fermentation at a standard cultivation temperature (30°C). The alcohol yield of OsMDHAR-expressing transgenic yeast during fermentation was approximately 25% (0.18 g·g-1) higher than that of WT yeast. Accordingly, OsMDHAR-expressing transgenic yeast showed prolonged survival during the environmental stresses produced during fermentation. These results suggest that heterologous OsMDHAR expression increases tolerance to reactive oxygen species-induced oxidative stress by improving cellular redox homeostasis and improves survival during fermentation, which enhances fermentative capacity. PMID:27392090

Adaptive laboratory evolution of Klebsiella pneumoniae for improving 2,3-butanediol production

PubMed Central

Li, Hongbiao; Zhang, Genlin; Dang, Yanyan

2016-01-01

ABSTRACT Microbial production of 2,3-butanediol is limited by the toxic components in the lignocellulose hydrolysate. To improve the 2,3-butanediol production via Klebsiella pneumoniae from cotton stalk hydrolysate, a method coupling a high tolerance of strain and detoxification of the hydrolysate was thus investigated in this study. The strain tolerance of K. pneumoniae to the cotton stalk hydrolysate was improved via an adaptive laboratory evolution, which involved a stepwise increase in the hydrolysate concentration in the medium. Compared with the initial strain, the resulting strain increased the biomass 3.2-fold in a medium of 20 g/L hydrolysate and produced 10.45 g/L of 2,3-butanediol at an optimal concentration of 60 g/L hydrolysate. After detoxification of cotton stalk hydrolysate, the cell metabolism of K. pneumoniae was further promoted, and the 2,3-butanediol production increased by 1.2 folds. Using fed-batch fermentation, the concentration of 2,3-butanediol reached 35.5 g/L with a yield of 0.43 g/g. The results demonstrated that the bioconversion of low-cost cotton stalk hydrolysate into 2,3-butanediol improves the economics of microbial 2,3-butanediol production. PMID:27442598

Stimulatory Effects of Arsenic-Tolerant Soil Fungi on Plant Growth Promotion and Soil Properties

PubMed Central

Srivastava, Pankaj Kumar; Shenoy, Belle Damodara; Gupta, Manjul; Vaish, Aradhana; Mannan, Shivee; Singh, Nandita; Tewari, Shri Krishna; Tripathi, Rudra Deo

2012-01-01

Fifteen fungi were obtained from arsenic-contaminated agricultural fields in West Bengal, India and examined for their arsenic tolerance and removal ability in our previous study. Of these, the four best arsenic-remediating isolates were tested for plant growth promotion effects on rice and pea in the present study. A greenhouse-based pot experiment was conducted using soil inocula of individual fungi. The results indicated a significant (P<0.05) increase in plant growth and improvement of soil properties in inoculated soils compared to the control. A significant increase in plant growth was recorded in treated soils and varied from 16–293%. Soil chemical and enzymatic properties varied from 20–222% and 34–760%, respectively, in inoculated soil. Plants inoculated with inocula of Westerdykella and Trichoderma showed better stimulatory effects on plant growth and soil nutrient availability than Rhizopus and Lasiodiplodia. These fungi improved soil nutrient content and enhanced plant growth. These fungi may be used as bioinoculants for plant growth promotion and improved soil properties in arsenic-contaminated agricultural soils. PMID:23047145

Stimulatory effects of arsenic-tolerant soil fungi on plant growth promotion and soil properties.

PubMed

Srivastava, Pankaj Kumar; Shenoy, Belle Damodara; Gupta, Manjul; Vaish, Aradhana; Mannan, Shivee; Singh, Nandita; Tewari, Shri Krishna; Tripathi, Rudra Deo

2012-01-01

Fifteen fungi were obtained from arsenic-contaminated agricultural fields in West Bengal, India and examined for their arsenic tolerance and removal ability in our previous study. Of these, the four best arsenic-remediating isolates were tested for plant growth promotion effects on rice and pea in the present study. A greenhouse-based pot experiment was conducted using soil inocula of individual fungi. The results indicated a significant (P<0.05) increase in plant growth and improvement of soil properties in inoculated soils compared to the control. A significant increase in plant growth was recorded in treated soils and varied from 16-293%. Soil chemical and enzymatic properties varied from 20-222% and 34-760%, respectively, in inoculated soil. Plants inoculated with inocula of Westerdykella and Trichoderma showed better stimulatory effects on plant growth and soil nutrient availability than Rhizopus and Lasiodiplodia. These fungi improved soil nutrient content and enhanced plant growth. These fungi may be used as bioinoculants for plant growth promotion and improved soil properties in arsenic-contaminated agricultural soils.

The effect of oxytocin nasal spray on social interaction deficits observed in young children with autism: a randomized clinical crossover trial.

PubMed

Yatawara, C J; Einfeld, S L; Hickie, I B; Davenport, T A; Guastella, A J

2016-09-01

Interventions for autism are limited. The synthetic hormone oxytocin may provide a potential treatment to improve core social and behavioral difficulties in autism, but its efficacy has yet to be evaluated in young children who potentially may benefit to a greater extent. We investigated the efficacy, tolerability and safety of oxytocin treatment in young children with autism using a double-blind, randomized, placebo-controlled, crossover, clinical trial. Thirty-one children with autism received 12 International Units (IU) of oxytocin and placebo nasal spray morning and night (24 IU per day) for 5 weeks, with a 4-week washout period between each treatment. Compared with placebo, oxytocin led to significant improvements on the primary outcome of caregiver-rated social responsiveness. Overall, nasal spray was well tolerated, and the most common reported adverse events were thirst, urination and constipation. This study is the first clinical trial to support the potential of oxytocin as an early intervention for young children with autism to help improve social interaction deficits.

The effect of oxytocin nasal spray on social interaction deficits observed in young children with autism: a randomized clinical crossover trial

PubMed Central

Yatawara, C J; Einfeld, S L; Hickie, I B; Davenport, T A; Guastella, A J

2016-01-01

Interventions for autism are limited. The synthetic hormone oxytocin may provide a potential treatment to improve core social and behavioral difficulties in autism, but its efficacy has yet to be evaluated in young children who potentially may benefit to a greater extent. We investigated the efficacy, tolerability and safety of oxytocin treatment in young children with autism using a double-blind, randomized, placebo-controlled, crossover, clinical trial. Thirty-one children with autism received 12 International Units (IU) of oxytocin and placebo nasal spray morning and night (24 IU per day) for 5 weeks, with a 4-week washout period between each treatment. Compared with placebo, oxytocin led to significant improvements on the primary outcome of caregiver-rated social responsiveness. Overall, nasal spray was well tolerated, and the most common reported adverse events were thirst, urination and constipation. This study is the first clinical trial to support the potential of oxytocin as an early intervention for young children with autism to help improve social interaction deficits. PMID:26503762

Improvement of activity and stability of chloroperoxidase by chemical modification

PubMed Central

Liu, Jian-Zhong; Wang, Min

2007-01-01

Background Enzymes show relative instability in solvents or at elevated temperature and lower activity in organic solvent than in water. These limit the industrial applications of enzymes. Results In order to improve the activity and stability of chloroperoxidase, chloroperoxidase was modified by citraconic anhydride, maleic anhydride or phthalic anhydride. The catalytic activities, thermostabilities and organic solvent tolerances of native and modified enzymes were compared. In aqueous buffer, modified chloroperoxidases showed similar Km values and greater catalytic efficiencies kcat/Km for both sulfoxidation and oxidation of phenol compared to native chloroperoxidase. Of these modified chloroperoxidases, citraconic anhydride-modified chloroperoxidase showed the greatest catalytic efficiency in aqueous buffer. These modifications of chloroperoxidase increased their catalytic efficiencies for sulfoxidation by 12%~26% and catalytic efficiencies for phenol oxidation by 7%~53% in aqueous buffer. However, in organic solvent (DMF), modified chloroperoxidases had lower Km values and higher catalytic efficiencies kcat/Km than native chloroperoxidase. These modifications also improved their thermostabilities by 1~2-fold and solvent tolerances of DMF. CD studies show that these modifications did not change the secondary structure of chloroperoxidase. Fluorescence spectra proved that these modifications changed the environment of tryptophan. Conclusion Chemical modification of epsilon-amino groups of lysine residues of chloroperoxidase using citraconic anhydride, maleic anhydride or phthalic anhydride is a simple and powerful method to enhance catalytic properties of enzyme. The improvements of the activity and stability of chloroperoxidase are related to side chain reorientations of aromatics upon both modifications. PMID:17511866

Oxybutynin as a treatment for generalized hyperhidrosis: a randomized, placebo-controlled trial.

PubMed

Schollhammer, M; Brenaut, E; Menard-Andivot, N; Pillette-Delarue, M; Zagnoli, A; Chassain-Le Lay, M; Sassolas, B; Jouan, N; Le Ru, Y; Abasq-Thomas, C; Greco, M; Penven, K; Roguedas-Contios, A M; Dupré-Goetghebeur, D; Gouedard, C; Misery, L; Le Gal, G

2015-11-01

Hyperhidrosis is a disorder that can impair quality of life. Localized treatments may be cumbersome and ineffective, and no systemic treatments have proven to be significantly beneficial. To evaluate the effectiveness and tolerance of low-dose oxybutynin for hyperhidrosis. We conducted a prospective, randomized, placebo-controlled trial. From June 2013 to January 2014, 62 patients with localized or generalized hyperhidrosis were enrolled. Oxybutynin was started at a dose of 2·5 mg per day and increased gradually to 7·5 mg per day. The primary outcome was defined as improvement of at least one point on the Hyperhidrosis Disease Severity Scale (HDSS). Dermatology Life Quality Index (DLQI) and tolerance were also reported. Most patients (83%) in our study had generalized hyperhidrosis. Oxybutynin was superior to placebo in improving the HDSS: 60% of patients treated with oxybutynin, compared with 27% of patients treated with placebo, improved at least one point on the HDSS (P = 0·009). The mean improvement in quality of life measured by DLQI was significantly better in the oxybutynin arm (6·9) than in the placebo arm (2·3). The most frequent side-effect was dry mouth, which was observed in 43% of the patients in the oxybutynin arm, compared with 11% in the placebo arm. Treatment with low-dose oxybutynin is effective in reducing symptoms of hyperhidrosis in generalized or localized forms. Side-effects were frequent but minor and mainly involved dry mouth. © 2015 British Association of Dermatologists.

An experimental evaluation of software redundancy as a strategy for improving reliability

NASA Technical Reports Server (NTRS)

Eckhardt, Dave E., Jr.; Caglayan, Alper K.; Knight, John C.; Lee, Larry D.; Mcallister, David F.; Vouk, Mladen A.; Kelly, John P. J.

1990-01-01

The strategy of using multiple versions of independently developed software as a means to tolerate residual software design faults is suggested by the success of hardware redundancy for tolerating hardware failures. Although, as generally accepted, the independence of hardware failures resulting from physical wearout can lead to substantial increases in reliability for redundant hardware structures, a similar conclusion is not immediate for software. The degree to which design faults are manifested as independent failures determines the effectiveness of redundancy as a method for improving software reliability. Interest in multi-version software centers on whether it provides an adequate measure of increased reliability to warrant its use in critical applications. The effectiveness of multi-version software is studied by comparing estimates of the failure probabilities of these systems with the failure probabilities of single versions. The estimates are obtained under a model of dependent failures and compared with estimates obtained when failures are assumed to be independent. The experimental results are based on twenty versions of an aerospace application developed and certified by sixty programmers from four universities. Descriptions of the application, development and certification processes, and operational evaluation are given together with an analysis of the twenty versions.

Comparing Tolerance of Ambiguity in Veterinary and Medical Students.

PubMed

Hancock, Jason; Hammond, Jennifer A; Roberts, Martin; Mattick, Karen

Current guidelines suggest that educators in both medical and veterinary professions should do more to ensure that students can tolerate ambiguity. Designing curricula to achieve this requires the ability to measure and understand differences in ambiguity tolerance among and within professional groups. Although scales have been developed to measure tolerance of ambiguity in both medical and veterinary professions, no comparative studies have been reported. We compared the tolerance of ambiguity of medical and veterinary students, hypothesizing that veterinary students would have higher tolerance of ambiguity, given the greater patient diversity and less well-established evidence base underpinning practice. We conducted a secondary analysis of questionnaire data from first- to fourth-year medical and veterinary students. Tolerance of ambiguity scores were calculated and compared using the TAMSAD scale (29 items validated for the medical student population), the TAVS scale (27 items validated for the veterinary student population), and a scale comprising the 22 items common to both scales. Using the TAMSAD and TAVS scales, medical students had a significantly higher mean tolerance of ambiguity score than veterinary students (56.1 vs. 54.1, p<.001 and 60.4 vs. 58.5, p=.002, respectively) but no difference was seen when only the 22 shared items were compared (56.1 vs. 57.2, p=.513). The results do not support our hypothesis and highlight that different findings can result when different tools are used. Medical students may have slightly higher tolerance of ambiguity than veterinary students, although this depends on the scale used.

Up-Regulation of HSFA2c and HSPs by ABA Contributing to Improved Heat Tolerance in Tall Fescue and Arabidopsis

PubMed Central

Wang, Xiuyun; Zhuang, Lili; Huang, Bingru

2017-01-01

Abscisic acid (ABA) is known to play roles in regulating plant tolerance to various abiotic stresses, but whether ABA’s effects on heat tolerance are associated with its regulation of heat stress transcription factors (HSFs) and heat shock proteins (HSPs) is not well documented. The objective of this study was to determine whether improved heat tolerance of tall fescue (Festuca arundinacea Schreb.) by ABA was through the regulation of HSFs and HSPs. ABA-responsive transcriptional factors, ABA-responsive element binding protein 3 (FaAREB3) and dehydration-responsive element binding protein 2A (FaDREB2A) of tall fescue, were able to bind to the cis-elements in the promoter of tall fescue heat stress transcription factor A2c (FaHSFA2c). Exogenous ABA (5 μM) application enhanced heat tolerance of tall fescue, as manifested by increased leaf photochemical efficiency and membrane stability under heat stress (37/32 °C, day/night). The expression levels of FaHSFA2c, several tall fescue HSPs (FaHSPs), and ABA-responsive transcriptional factors were up-regulated in plants treated with ABA. Deficiency of Arabidopsis heat stress transcription factor A2 (AtHSFA2) suppressed ABA-induction of AtHSPs expression and ABA-improved heat tolerance in Arabidopsis. These results suggested that HSFA2 plays an important role in ABA-mediated plant heat tolerance, and FaAREB3 and FaDREB2A may function as upstream trans-acting factors and regulate transcriptional activity of FaHSFA2c and the downstream FaHSPs, leading to improved heat tolerance. PMID:28914758

Improved tolerance toward fungal diseases in transgenic Cavendish banana (Musa spp. AAA group) cv. Grand Nain.

PubMed

Vishnevetsky, Jane; White, Thomas L; Palmateer, Aaron J; Flaishman, Moshe; Cohen, Yuval; Elad, Yigal; Velcheva, Margarita; Hanania, Uri; Sahar, Nachman; Dgani, Oded; Perl, Avihai

2011-02-01

The most devastating disease currently threatening to destroy the banana industry worldwide is undoubtedly Sigatoka Leaf spot disease caused by Mycosphaerella fijiensis. In this study, we developed a transformation system for banana and expressed the endochitinase gene ThEn-42 from Trichoderma harzianum together with the grape stilbene synthase (StSy) gene in transgenic banana plants under the control of the 35S promoter and the inducible PR-10 promoter, respectively. The superoxide dismutase gene Cu,Zn-SOD from tomato, under control of the ubiquitin promoter, was added to this cassette to improve scavenging of free radicals generated during fungal attack. A 4-year field trial demonstrated several transgenic banana lines with improved tolerance to Sigatoka. As the genes conferring Sigatoka tolerance may have a wide range of anti-fungal activities we also inoculated the regenerated banana plants with Botrytis cinerea. The best transgenic lines exhibiting Sigatoka tolerance were also found to have tolerance to B. cinerea in laboratory assays.

The Use of Ammonium Formate as a Mobile-Phase Modifier for LC-MS/MS Analysis of Tryptic Digests

PubMed Central

Johnson, Darryl; Boyes, Barry; Orlando, Ron

2013-01-01

A major challenge facing current mass spectrometry (MS)-based proteomics research is the large concentration range displayed in biological systems, which far exceeds the dynamic range of commonly available mass spectrometers. One approach to overcome this limitation is to improve online reversed-phase liquid chromatography (RP-LC) separation methodologies. LC mobile-phase modifiers are used to improve peak shape and increase sample load tolerance. Trifluoroacetic acid (TFA) is a commonly used mobile-phase modifier, as it produces peptide separations that are far superior to other additives. However, TFA leads to signal suppression when incorporated with electrospray ionization (ESI), and thus, other modifiers, such as formic acid (FA), are used for LC-MS applications. FA exhibits significantly less signal suppression, but is not as effective of a modifier as TFA. An alternative mobile-phase modifier is the combination of FA and ammonium formate (AF), which has been shown to improve peptide separations. The ESI-MS compatibility of this modifier has not been investigated, particularly for proteomic applications. This work compares the separation metrics of mobile phases modified with FA and FA/AF and explores the use of FA/AF for the LC-MS analysis of tryptic digests. Standard tryptic-digest peptides were used for comparative analysis of peak capacity and sample load tolerance. The compatibility of FA/AF in proteomic applications was examined with the analysis of soluble proteins from canine prostate carcinoma tissue. Overall, the use of FA/AF improved online RP-LC separations and led to significant increases in peptide identifications with improved protein sequence coverage. PMID:24294112

The use of ammonium formate as a mobile-phase modifier for LC-MS/MS analysis of tryptic digests.

PubMed

Johnson, Darryl; Boyes, Barry; Orlando, Ron

2013-12-01

A major challenge facing current mass spectrometry (MS)-based proteomics research is the large concentration range displayed in biological systems, which far exceeds the dynamic range of commonly available mass spectrometers. One approach to overcome this limitation is to improve online reversed-phase liquid chromatography (RP-LC) separation methodologies. LC mobile-phase modifiers are used to improve peak shape and increase sample load tolerance. Trifluoroacetic acid (TFA) is a commonly used mobile-phase modifier, as it produces peptide separations that are far superior to other additives. However, TFA leads to signal suppression when incorporated with electrospray ionization (ESI), and thus, other modifiers, such as formic acid (FA), are used for LC-MS applications. FA exhibits significantly less signal suppression, but is not as effective of a modifier as TFA. An alternative mobile-phase modifier is the combination of FA and ammonium formate (AF), which has been shown to improve peptide separations. The ESI-MS compatibility of this modifier has not been investigated, particularly for proteomic applications. This work compares the separation metrics of mobile phases modified with FA and FA/AF and explores the use of FA/AF for the LC-MS analysis of tryptic digests. Standard tryptic-digest peptides were used for comparative analysis of peak capacity and sample load tolerance. The compatibility of FA/AF in proteomic applications was examined with the analysis of soluble proteins from canine prostate carcinoma tissue. Overall, the use of FA/AF improved online RP-LC separations and led to significant increases in peptide identifications with improved protein sequence coverage.

Difference in Yield and Physiological Features in Response to Drought and Salinity Combined Stress during Anthesis in Tibetan Wild and Cultivated Barleys

PubMed Central

Ahmed, Imrul Mosaddek; Cao, Fangbin; Zhang, Mian; Chen, Xianhong; Zhang, Guoping; Wu, Feibo

2013-01-01

Soil salinity and drought are the two most common and frequently co-occurring abiotic stresses constraining crop growth and productivity. Greenhouse pot experiments were conducted to investigate the tolerance potential and mechanisms of Tibetan wild barley genotypes (XZ5, drought-tolerant; XZ16, salinity/aluminum tolerant) during anthesis compared with salinity-tolerant cv CM72 in response to separate and combined stresses (D+S) of drought (4% soil moisture, D) and salinity (S). Under salinity stress alone, plants had higher Na+ concentrations in leaves than in roots and stems. Importantly, XZ5 and XZ16 had substantially increased leaf K+ concentrations; XZ16 was more efficient in restricting Na+ loading in leaf and maintained a lower leaf Na+/K+ ratio. Moreover, a significant decrease in cell membrane stability index (CMSI) and an increase in malondialdehyde (MDA) were accompanied by a dramatic decrease in total biomass under D+S treatment. We demonstrated that glycine-betaine and soluble sugars increased significantly in XZ5 and XZ16 under all stress conditions, along with increases in protease activity and soluble protein contents. Significant increases were seen in reduced ascorbate (ASA) and reduced glutathione (GSH) contents, and in activities of H+K+-, Na+K+-, Ca++Mg++-, total- ATPase, and antioxidant enzymes under D+S treatment in XZ5 and XZ16 compared to CM72. Compared with control, all stress treatments significantly reduced grain yield and 1000-grain weight; however, XZ5 and XZ16 were less affected than CM72. Our results suggest that high tolerance to D+S stress in XZ5 and XZ16 is closely related to the lower Na+/K+ ratio, and enhanced glycine-betaine and soluble protein and sugar contents, improved protease, ATPase activities and antioxidative capacity for scavenging reactive oxygen species during anthesis. These results may provide novel insight into the potential responses associated with increasing D+S stress in wild barley genotypes. PMID:24205003

Some physiological aspects of artificial gravity. [gravitational effects on human orthostatic tolerance and physical fitness

NASA Technical Reports Server (NTRS)

Cramer, D. B.; Graybiel, A.

1973-01-01

The effects of increasing artificial gravity exposure on four aspects of physiological fitness are examined in four young men who, prior to exposure, were deconditioned with bed rest and water immersion. The four aspects of physiological fitness are orthostatic tolerance, exercise tolerance, forearm endurance, and maximum strength. Orthostatic tolerance was sharply reduced by deconditioning and was substantially improved by walking in simulated lunar gravity (1/6 g) for 2.5 hours daily for 7 days or by walking in 1/2 g and 1 g for 1 hour daily for 3 days. Exercise tolerance was also sharply reduced by deconditioning but did not significantly improve with increasing g-exposure. Walking in 1 g for 1 hour daily for 3 days raised exercise tolerance only a little above the low produced by deconditioning. Forearm endurance and maximum strength were relatively unaffected by deconditioning and subsequent g-exposure.

Genetic analysis of tolerance to the root lesion nematode Pratylenchus neglectus in the legume Medicago littoralis.

PubMed

Oldach, Klaus H; Peck, David M; Nair, Ramakrishnan M; Sokolova, Maria; Harris, John; Bogacki, Paul; Ballard, Ross

2014-04-17

The nematode Pratylenchus neglectus has a wide host range and is able to feed on the root systems of cereals, oilseeds, grain and pasture legumes. Under the Mediterranean low rainfall environments of Australia, annual Medicago pasture legumes are used in rotation with cereals to fix atmospheric nitrogen and improve soil parameters. Considerable efforts are being made in breeding programs to improve resistance and tolerance to Pratylenchus neglectus in the major crops wheat and barley, which makes it vital to develop appropriate selection tools in medics. A strong source of tolerance to root damage by the root lesion nematode (RLN) Pratylenchus neglectus had previously been identified in line RH-1 (strand medic, M. littoralis). Using RH-1, we have developed a single seed descent (SSD) population of 138 lines by crossing it to the intolerant cultivar Herald. After inoculation, RLN-associated root damage clearly segregated in the population. Genetic analysis was performed by constructing a genetic map using simple sequence repeat (SSR) and gene-based SNP markers. A highly significant quantitative trait locus (QTL), QPnTolMl.1, was identified explaining 49% of the phenotypic variation in the SSD population. All SSRs and gene-based markers in the QTL region were derived from chromosome 1 of the sequenced genome of the closely related species M. truncatula. Gene-based markers were validated in advanced breeding lines derived from the RH-1 parent and also a second RLN tolerance source, RH-2 (M. truncatula ssp. tricycla). Comparative analysis to sequenced legume genomes showed that the physical QTL interval exists as a synteny block in Lotus japonicus, common bean, soybean and chickpea. Furthermore, using the sequenced genome information of M. truncatula, the QTL interval contains 55 genes out of which five are discussed as potential candidate genes responsible for the mapped tolerance. The closely linked set of SNP-based PCR markers is directly applicable to select for two different sources of RLN tolerance in breeding programs. Moreover, genome sequence information has allowed proposing candidate genes for further functional analysis and nominates QPnTolMl.1 as a target locus for RLN tolerance in economically important grain legumes, e.g. chickpea.

Natto and viscous vegetables in a Japanese-style breakfast improved insulin sensitivity, lipid metabolism and oxidative stress in overweight subjects with impaired glucose tolerance.

PubMed

Taniguchi-Fukatsu, Akiko; Yamanaka-Okumura, Hisami; Naniwa-Kuroki, Yuko; Nishida, Yuka; Yamamoto, Hironori; Taketani, Yutaka; Takeda, Eiji

2012-04-01

We previously suggested that the consumption of natto and viscous vegetables as part of a Japanese-style meal based on white rice (WR) reduced postprandial glucose and insulin levels in healthy subjects. The aim of the present study was to assess whether a single breakfast of natto and viscous vegetables or the same breakfast consumed for 2 weeks could improve glucose control, insulin sensitivity, lipid metabolism and oxidative stress in overweight subjects with impaired glucose tolerance (IGT). A total of eleven free-living subjects with IGT followed a randomised, crossover breakfast intervention for 2 weeks. The test meal included boiled WR with natto (viscous fermented soyabeans), Japanese yam and okra. The control meal included WR with non-viscous boiled soyabeans, potatoes and broccoli. Both meals contained comparable amounts of carbohydrate, fat, protein and fibre. The test meal reduced acute glucose and insulin responses compared to the control meal in the study participants. Insulin sensitivity was assessed using the composite insulin sensitivity index (CISI) after both the test and control meal periods. The test meal resulted in improvements in CISI compared to the baseline, whereas no significant changes were observed after the control meal period. Serum levels of both total and LDL-cholesterol were assessed before and after the test meal period and found to decrease significantly. There was also a tendency towards reduced serum malondialdehyde-modified LDL and N(ɛ)-carboxymethyllysine. No differences were observed in the measures of chronic glycaemic control. Thus, we conclude that a breakfast of natto and viscous vegetables consumed for 2 weeks improves insulin sensitivity, serum lipid and oxidative stress.

OsSUV3 dual helicase functions in salinity stress tolerance by maintaining photosynthesis and antioxidant machinery in rice (Oryza sativa L. cv. IR64).

PubMed

Tuteja, Narendra; Sahoo, Ranjan Kumar; Garg, Bharti; Tuteja, Renu

2013-10-01

To overcome the salinity-induced loss of crop yield, a salinity-tolerant trait is required. The SUV3 helicase is involved in the regulation of RNA surveillance and turnover in mitochondria, but the helicase activity of plant SUV3 and its role in abiotic stress tolerance have not been reported so far. Here we report that the Oryza sativa (rice) SUV3 protein exhibits DNA and RNA helicase, and ATPase activities. Furthermore, we report that SUV3 is induced in rice seedlings in response to high levels of salt. Its expression, driven by a constitutive cauliflower mosaic virus 35S promoter in IR64 transgenic rice plants, confers salinity tolerance. The T1 and T2 sense transgenic lines showed tolerance to high salinity and fully matured without any loss in yields. The T2 transgenic lines also showed tolerance to drought stress. These results suggest that the introduced trait is functional and stable in transgenic rice plants. The rice SUV3 sense transgenic lines showed lesser lipid peroxidation, electrolyte leakage and H2 O2 production, along with higher activities of antioxidant enzymes under salinity stress, as compared with wild type, vector control and antisense transgenic lines. These results suggest the existence of an efficient antioxidant defence system to cope with salinity-induced oxidative damage. Overall, this study reports that plant SUV3 exhibits DNA and RNA helicase and ATPase activities, and provides direct evidence of its function in imparting salinity stress tolerance without yield loss. The possible mechanism could be that OsSUV3 helicase functions in salinity stress tolerance by improving photosynthesis and antioxidant machinery in transgenic rice. © 2013 The Authors The Plant Journal © 2013 John Wiley & Sons Ltd.

Improved robustness of an ethanologenic yeast strain through adaptive evolution in acetic acid is associated with its enzymatic antioxidant ability.

PubMed

Gurdo, N; Novelli Poisson, G F; Juárez, Á B; Ríos de Molina, M C; Galvagno, M A

2018-05-16

To investigate multiple tolerance of Saccharomyces cerevisiae obtained through a laboratory strategy of adaptive evolution in acetic acid, its relation with enzymatic ROS detoxification and bioethanol 2G production. After adaptive evolution in acetic acid, a clone (Y8A) was selected for its tolerance to high acetic acid concentrations (13 g l -1 ) in batch cultures. Y8A was resistant to multiple stresses: osmotic, thermic, oxidative, saline, ethanol, organic acid, phenolic compounds and slow freeze-thawing cycles. Also, Y8A was able to maintain redox homeostasis under oxidative stress, whereas the isogenic parental strain (Y8) could not, indicating higher basal activity levels of antioxidative enzyme Catalase (CAT) and Gluthatione-S-Transferase (GST) in Y8A. Y8A reached higher bioethanol levels in a fermentation medium containing up to 8 g l -1 of acetic acid when compared to parental strain Y8. A multiple-stress-tolerant clone was obtained using adaptive evolution in acetic acid. Stress cross-tolerance could be explained by its enzymatic antioxidative capacity, namely CAT and GST. We demonstrate that adaptive evolution used in S. cerevisiae was a useful strategy to obtain a yeast clone tolerant to multiple stresses. At the same time, our findings support the idea that tolerance to oxidative stress is the common basis for stress co-tolerance, which is related to an increase in the specific enzymes CAT and GST but not in Superoxide dismutase (SOD), emphasizing the fact that detoxification of H 2 O 2 and not O 2 . is a key condition for multiple stress tolerance in S. cerevisiae. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Gibberellin Deficiency Confers Both Lodging and Drought Tolerance in Small Cereals

PubMed Central

Plaza-Wüthrich, Sonia; Blösch, Regula; Rindisbacher, Abiel; Cannarozzi, Gina; Tadele, Zerihun

2016-01-01

Tef [Eragrostis tef (Zucc.) Trotter] and finger millet [Eleusine coracana Gaertn] are staple cereal crops in Africa and Asia with several desirable agronomic and nutritional properties. Tef is becoming a life-style crop as it is gluten-free while finger millet has a low glycemic index which makes it an ideal food for diabetic patients. However, both tef and finger millet have extremely low grain yields mainly due to moisture scarcity and susceptibility of the plants to lodging. In this study, the effects of gibberellic acid (GA) inhibitors particularly paclobutrazol (PBZ) on diverse physiological and yield-related parameters were investigated and compared to GA mutants in rice (Oryza sativa L.). The application of PBZ to tef and finger millet significantly reduced the plant height and increased lodging tolerance. Remarkably, PBZ also enhanced the tolerance of both tef and finger millet to moisture deficit. Under moisture scarcity, tef plants treated with PBZ did not exhibit drought-related symptoms and their stomatal conductance was unaltered, leading to higher shoot biomass and grain yield. Semi-dwarf rice mutants altered in GA biosynthesis, were also shown to have improved tolerance to dehydration. The combination of traits (drought tolerance, lodging tolerance and increased yield) that we found in plants with altered GA pathway is of importance to breeders who would otherwise rely on extensive crossing to introgress each trait individually. The key role played by PBZ in the tolerance to both lodging and drought calls for further studies using mutants in the GA biosynthesis pathway in order to obtain candidate lines which can be incorporated into crop-breeding programs to create lodging tolerant and climate-smart crops. PMID:27242844

Cost-effectiveness modeling for neuropathic pain treatments: investigating the relative importance of parameters using an open-source model.

PubMed

Hirst, Matthew; Bending, Matthew W; Baio, Gianluca; Yesufu-Udechuku, Amina; Dunlop, William C N

2018-06-08

The study objective was to develop an open-source replicate of a cost-effectiveness model developed by National Institute for Health and Care (NICE) in order to explore uncertainties in health economic modeling of novel pharmacological neuropathic pain treatments. The NICE model, consisting of a decision tree with branches for discrete levels of pain relief and adverse event (AE) severities, was replicated using R and used to compare a hypothetical neuropathic pain drug to pregabalin. Model parameters were sourced from NICE's clinical guidelines and associated with probability distributions to account for underlying uncertainty. A simulation-based scenario analysis was conducted to assess how uncertainty in efficacy and AEs affected the net monetary benefit (NMB) for the hypothetical treatment at a cost-effectiveness threshold of £20,000 per QALY. Relative to pregabalin, an increase in efficacy was associated with greater NMB than an improvement in tolerability. A greater NMB was observed when efficacy was marginally higher than that of pregabalin while maintaining the same level of AEs than when efficacy was equivalent to pregabalin but with a more substantial reduction in AEs. In the latter scenario, the NMB was only positive at a low cost-effectiveness threshold. The replicate model shares the limitations described in the NICE guidelines. There is a lack of support in scientific literature for the assumption that increased efficacy is associated with a greater reduction in tolerability. The replicate model also included a single comparator, unlike the NICE model. Pain relief is a stronger driver of NMB than tolerability at a cost-effectiveness threshold of £20,000 per QALY. Health technology assessment decisions which are influenced by NICE's model may reward efficacy gains even if they are associated with more severe AEs. This contrasts with recommendations from clinical guidelines for neuropathic pain which place more equal weighting on improvements in efficacy and tolerability as value drivers.

Physiological investigation of C4-phosphoenolpyruvate-carboxylase-introduced rice line shows that sucrose metabolism is involved in the improved drought tolerance.

PubMed

Zhang, Chen; Li, Xia; He, Yafei; Zhang, Jinfei; Yan, Ting; Liu, Xiaolong

2017-06-01

We compared the drought tolerance of wild-type (WT) and transgenic rice plants (PC) over-expressing the maize C 4 PEPC gene, which encodes phosphoenolpyruvate carboxylase (PEPC, EC 4.1.1.31) gene, and evaluated the roles of saccharide and sugar-related enzymes in the drought response. Pot-grown seedlings were subjected to real drought conditions outdoors, and the yield components were compared between PC and untransformed wild-type (WT) plants. The stable yield from PC plants was associated with higher net photosynthetic rate under the real drought treatment. The physiological characters of WT and PC seedlings under a simulated drought treatment (25% (w/v) polyethylene glycol-6000 for 3 h; PEG 6000 treatment) were analyzed in detail for the early response of drought. The relative water content was higher in PC than in WT, and PEPC activity and the C 4 -PEPC transcript level in PC were elevated under the simulated drought conditions. The endogenous saccharide responses also differed between PC and WT under simulated drought stress. The higher sugar decomposition rate in PC than in WT under drought analog stress was related to the increased activities of sucrose phosphate synthase, sucrose synthase, acid invertase, and neutral invertase, increased transcript levels of VIN1, CIN1, NIN1, SUT2, SUT4, and SUT5, and increased activities of superoxide dismutase and peroxidase in the leaves. The greater antioxidant defense capacity of PC and its relationship with saccharide metabolism was one of the reasons for the improved drought tolerance. In conclusion, PEPC effectively alleviated oxidative damage and enhanced the drought tolerance in rice plants, which were more related to the increase of the endogenous saccharide decomposition. These findings show that components of C 4 photosynthesis can be used to increase the yield of rice under drought conditions. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Sorghum Landrace Collections from Cooler Regions of the World Exhibit Magnificent Genetic Differentiation and Early Season Cold Tolerance.

PubMed

Maulana, Frank; Weerasooriya, Dilooshi; Tesso, Tesfaye

2017-01-01

Cold temperature is an important abiotic stress affecting sorghum production in temperate regions. It reduces seed germination, seedling emergence and seedling vigor thus limiting the production of the crop both temporally and spatially. The objectives of this study were (1) to assess early season cold temperature stress response of sorghum germplasm from cooler environments and identify sources of tolerance for use in breeding programs, (2) to determine population structure and marker-trait association among these germplasms for eventual development of marker tools for improving cold tolerance. A total of 136 sorghum accessions from cooler regions of the world were phenotyped for seedling growth characteristics under cold temperature imposed through early planting. The accessions were genotyped using 67 simple sequence repeats markers spanning all ten linkage groups of sorghum, of which 50 highly polymorphic markers were used in the analysis. Genetic diversity and population structure analyses sorted the population into four subpopulations. Several accessions distributed in all subpopulations showed either better or comparable level of tolerance to the standard cold tolerance source, Shan qui red. Association analysis between the markers and seedling traits identified markers Xtxp 34, Xtxp 88, and Xtxp 319 as associated with seedling emergence, Xtxp 211 and Xtxp 304 with seedling dry weight, and Xtxp 20 with seedling height. The markers were detected on chromosomes previously found to harbor QTLs associated with cold tolerance in sorghum. Once validated these may serve as genomic tools in marker-assisted breeding or for screening larger pool of genotypes to identify additional sources of cold tolerance.

Sorghum Landrace Collections from Cooler Regions of the World Exhibit Magnificent Genetic Differentiation and Early Season Cold Tolerance

PubMed Central

Maulana, Frank; Weerasooriya, Dilooshi; Tesso, Tesfaye

2017-01-01

Cold temperature is an important abiotic stress affecting sorghum production in temperate regions. It reduces seed germination, seedling emergence and seedling vigor thus limiting the production of the crop both temporally and spatially. The objectives of this study were (1) to assess early season cold temperature stress response of sorghum germplasm from cooler environments and identify sources of tolerance for use in breeding programs, (2) to determine population structure and marker-trait association among these germplasms for eventual development of marker tools for improving cold tolerance. A total of 136 sorghum accessions from cooler regions of the world were phenotyped for seedling growth characteristics under cold temperature imposed through early planting. The accessions were genotyped using 67 simple sequence repeats markers spanning all ten linkage groups of sorghum, of which 50 highly polymorphic markers were used in the analysis. Genetic diversity and population structure analyses sorted the population into four subpopulations. Several accessions distributed in all subpopulations showed either better or comparable level of tolerance to the standard cold tolerance source, Shan qui red. Association analysis between the markers and seedling traits identified markers Xtxp34, Xtxp88, and Xtxp319 as associated with seedling emergence, Xtxp211 and Xtxp304 with seedling dry weight, and Xtxp20 with seedling height. The markers were detected on chromosomes previously found to harbor QTLs associated with cold tolerance in sorghum. Once validated these may serve as genomic tools in marker-assisted breeding or for screening larger pool of genotypes to identify additional sources of cold tolerance. PMID:28536596

Engineering transcription factors to improve tolerance against alkane biofuels in Saccharomyces cerevisiae.

PubMed

Ling, Hua; Pratomo Juwono, Nina Kurniasih; Teo, Wei Suong; Liu, Ruirui; Leong, Susanna Su Jan; Chang, Matthew Wook

2015-01-01

Biologically produced alkanes can be used as 'drop in' to existing transportation infrastructure as alkanes are important components of gasoline and jet fuels. Despite the reported microbial production of alkanes, the toxicity of alkanes to microbial hosts could pose a bottleneck for high productivity. In this study, we aimed to improve the tolerance of Saccharomyces cerevisiae, a model eukaryotic host of industrial significance, to alkane biofuels. To increase alkane tolerance in S. cerevisiae, we sought to exploit the pleiotropic drug resistance (Pdr) transcription factors Pdr1p and Pdr3p, which are master regulators of genes with pleiotropic drug resistance elements (PDREs)-containing upstream sequences. Wild-type and site-mutated Pdr1p and Pdr3p were expressed in S. cerevisiae BY4741 pdr1Δ pdr3Δ (BYL13). The point mutations of PDR1 (F815S) and PDR3 (Y276H) in BYL13 resulted in the highest tolerance to C10 alkane, and the expression of wild-type PDR3 in BYL13 led to the highest tolerance to C11 alkane. To identify and verify the correlation between the Pdr transcription factors and tolerance improvement, we analyzed the expression patterns of genes regulated by the Pdr transcription factors in the most tolerant strains against C10 and C11 alkanes. Quantitative PCR results showed that the Pdr transcription factors differentially regulated genes associated with multi-drug resistance, stress responses, and membrane modifications, suggesting different extents of intracellular alkane levels, reactive oxygen species (ROS) production and membrane integrity. We further showed that (i) the expression of Pdr1mt1 + Pdr3mt reduced intracellular C10 alkane by 67 % and ROS by 53 %, and significantly alleviated membrane damage; and (ii) the expression of the Pdr3wt reduced intracellular C11 alkane by 72 % and ROS by 21 %. Alkane transport assays also revealed that the reduction of alkane accumulation was due to higher export (C10 and C11 alkanes) and lower import (C11 alkane). We improved yeast's tolerance to alkane biofuels by modulating the expression of the wild-type and site-mutated Pdr1p and Pdr3p, and extensively identified the correlation between Pdr transcription factors and tolerance improvement by analyzing gene patterns, alkane transport, ROS, and membrane integrity. These findings provide valuable insights into manipulating transcription factors in yeast for improved alkane tolerance and productivity.

A Controlled Trial of CPAP Therapy on Metabolic Control in Individuals with Impaired Glucose Tolerance and Sleep Apnea

PubMed Central

Weinstock, Tanya G.; Wang, Xuelei; Rueschman, Michael; Ismail-Beigi, Faramarz; Aylor, Joan; Babineau, Denise C.; Mehra, Reena; Redline, Susan

2012-01-01

Study Objectives: To address whether treatment of sleep apnea improves glucose tolerance. Design: Randomized, double-blind crossover study. Setting: Sleep clinic referrals. Patients: 50 subjects with moderate to severe sleep apnea (AHI > 15) and impaired glucose tolerance. Interventions: Subjects were randomized to 8 weeks of CPAP or sham CPAP, followed by the alternate therapy after a one-month washout. After each treatment, subjects underwent 2-hour OGTT, polysomnography, actigraphy, and measurements of indices of glucose control. Measurements and Results: The primary outcome was normalization of the mean 2-h OGTT; a secondary outcome was improvement in the Insulin Sensitivity Index (ISI (0,120). Subjects were 42% men, mean age of 54 (10), BMI of 39 (8), and AHI of 44 (27). Baseline fasting glucose was 104 (12), and mean 2-h OGTT was 110 (57) mg/dL. Seven subjects normalized their mean 2-h OGTT after CPAP but not after sham CPAP, while 5 subjects normalized after sham CPAP but not after CPAP. Overall, there was no improvement in ISI (0,120) between CPAP and sham CPAP (3.6%; 95% CI: [-2.2%, 9.7%]; P = 0.22). However, in those subjects with baseline AHI ≥ 30 (n = 25), there was a 13.3% (95% CI: [5.2%, 22.1%]; P < 0.001) improvement in ISI (0,120) and a 28.7% (95%CI: [-46.5%, −10.9%], P = 0.002) reduction in the 2-h insulin level after CPAP compared to sham CPAP. Conclusions: This study did not show that IGT normalizes after CPAP in subjects with moderate sleep apnea and obesity. However, insulin sensitivity improved in those with AHI ≥ 30, suggesting beneficial metabolic effects of CPAP in severe sleep apnea. Clinical Trials Information: ClinicalTrials.gov Identifier: NCT01385995. Citation: Weinstock TG; Wang X; Rueschman M; Ismail-Beigi F; Aylor J; Babineau DC; Mehra R; Redline S. A controlled trial of CPAP therapy on metabolic control in individuals with impaired glucose tolerance and sleep apnea. SLEEP 2012;35(5):617-625. PMID:22547887

Overexpression of a specific soybean GmGSTU4 isoenzyme improves diphenyl ether and chloroacetanilide herbicide tolerance of transgenic tobacco plants.

PubMed

Benekos, Kostantinos; Kissoudis, Christos; Nianiou-Obeidat, Irini; Labrou, Nikolaos; Madesis, Panagiotis; Kalamaki, Mary; Makris, Antonis; Tsaftaris, Athanasios

2010-10-01

Plant glutathione transferases (GSTs) superfamily consists of multifunctional enzymes and forms a major part of the plants herbicide detoxification enzyme network. The tau class GST isoenzyme GmGSTU4 from soybean, exhibits catalytic activity towards the diphenyl ether herbicide fluorodifen and is active as glutathione-dependent peroxidase (GPOX). Transgenic tobacco plants of Basmas cultivar were generated via Agrobacterium transformation. The aim was to evaluate in planta, GmGSTU4's role in detoxifying the diphenyl ether herbicides fluorodifen and oxyfluorfen and the chloroacetanilides alachlor and metolachlor. Transgenic tobacco plants were verified by PCR and Southern blot hybridization and expression of GmGSTU4 was determined by RT-PCR. Leaf extracts from transgenic plants showed moderate increase in GST activity towards CDNB and a significant increase towards fluorodifen and alachlor, and at the same time an increased GPOX activity towards cumene hydroperoxide. GmGSTU4 overexpressing plants when treated with 200 μM fluorodifen or oxyfluorfen exhibited reduced relative electrolyte leakage compared to wild type plants. Moreover all GmGSTU4 overexpressing lines exhibited significantly increased tolerance towards alachlor when grown in vitro at 7.5 mg/L alachlor compared to wild type plants. No significant increased tolerance was observed to metolachlor. These results confirm the contribution of this particular GmGSTU4 isoenzyme from soybean in the detoxification of fluorodifen and alachlor, and provide the basis towards the development of transgenic plants with improved phytoremediation capabilities for future use in environmental cleanup of herbicides. Copyright © 2010 Elsevier B.V. All rights reserved.

Versatility of azelaic acid 15% gel in treatment of inflammatory acne vulgaris.

PubMed

Thiboutot, Diane

2008-01-01

Azelaic acid (AzA) 15% gel is approved for the treatment of rosacea in the US, but also has approval for the treatment of acne vulgaris in many European countries where it has demonstrated success. Two randomized, multicenter, controlled clinical trials compared the effects of AzA 15% gel with those of topical benzoyl peroxide 5% or topical clindamycin 1%, all using a twice-daily dosing regimen. The primary endpoint in the intent-to-treat analysis was a reduction in inflammatory papules and pustules. AzA 15% gel resulted in a 70% to 71% median reduction of facial papules and pustules compared with a 77% reduction with benzoyl peroxide 5% gel and a 63% reduction with clindamycin. AzA 15% gel was well-tolerated. In addition, a 1-year European observational study conducted by dermatologists in private practice evaluated the safety and efficacy of AzA 15% gel used as monotherapy or in combination with other agents in more than 1200 patients with acne. Most physicians (81.9%) described an improvement in patients' symptoms after an average of 34.6 days, and 93.9% of physicians reported patient improvement after an average of 73.1 days. Both physicians and patients assessed AzA 15% gel to be effective with 74% of patients being "very satisfied" at the end of therapy. AzA 15% gel was considered "well-tolerated" or "very well-tolerated" by 95.7% of patients. The majority of patients were more satisfied with AzA than with previous therapies. AzA 15% gel represents a new therapeutic option for the treatment of acne vulgaris.

Diabetes-associated microbiota in fa/fa rats is modified by Roux-en-Y gastric bypass

PubMed Central

Arora, Tulika; Seyfried, Florian; Docherty, Neil G; Tremaroli, Valentina; le Roux, Carel W; Perkins, Rosie; Bäckhed, Fredrik

2017-01-01

Roux-en-Y gastric bypass (RYGB) and duodenal jejunal bypass (DJB), two different forms of bariatric surgery, are associated with improved glucose tolerance, but it is not clear whether the gut microbiota contributes to this effect. Here we used fa/fa rats as a model of impaired glucose tolerance to investigate whether (i) the microbiota varies between fa/fa and nondiabetic fa/+ rats; (ii) the microbiota of fa/fa rats is affected by RYGB and/or DJB; and (iii) surgically induced microbiota alterations contribute to glucose metabolism. We observed a profound expansion of Firmicutes (specifically, Lactobacillus animalis and Lactobacillus reuteri) in the small intestine of diabetic fa/fa compared with nondiabetic fa/+ rats. RYGB-, but not DJB-, treated fa/fa rats exhibited greater microbiota diversity in the ileum and lower L. animalis and L. reuteri abundance compared with sham-operated fa/fa rats in all intestinal segments, and their microbiota composition resembled that of unoperated fa/+ rats. To investigate the functional role of RYGB-associated microbiota alterations, we transferred microbiota from sham- and RYGB-treated fa/fa rats to germ-free mice. The metabolic phenotype of RYGB-treated rats was not transferred by the transplant of ileal microbiota. In contrast, postprandial peak glucose levels were lower in mice that received cecal microbiota from RYGB- versus sham-operated rats. Thus, diabetes-associated microbiota alterations in fa/fa rats can be modified by RYGB, and modifications in the cecal microbiota may partially contribute to improved glucose tolerance after RYGB. PMID:28524868

Modafinil in the treatment of excessive sleepiness

PubMed Central

Schwartz, Jonathan RL

2008-01-01

The wake-promoting agent modafinil is approved for the treatment of excessive sleepiness associated with obstructive sleep apnea (OSA), shift work disorder (SWD), and narcolepsy. In OSA, modafinil is recommended for use as an adjunct to standard therapies that treat the underlying airway obstruction. This article reviews the literature on modafinil (pharmacology, pharmacokinetics, efficacy, tolerability, and abuse potential), with emphasis on use of modafinil in the treatment of excessive sleepiness in patients with OSA, SWD, and narcolepsy. In large-scale, double-blind, placebo-controlled studies, modafinil improved objectively determined sleep latency, improved overall clinical condition related to severity of sleepiness, and reduced patient-reported sleepiness. Improvements in wakefulness were accompanied by improvements in behavioral alertness, functional status, and health-related quality of life. In patients with SWD, diary data showed modafinil reduced the maximum level of sleepiness during night shift work, level of sleepiness during the commute home, and incidence of accidents or near-accidents during the commute home when compared with placebo. Modafinil was well tolerated, without adversely affecting cardiovascular parameters or scheduled sleep. These findings and those of extension studies which reported improvements were maintained suggest modafinil has a beneficial effect on daily life and well-being in patients with excessive sleepiness associated with OSA, SWD, or narcolepsy. PMID:19920895

Topical adapalene gel 0.1% vs. isotretinoin gel 0.05% in the treatment of acne vulgaris: a randomized open-label clinical trial.

PubMed

Ioannides, D; Rigopoulos, D; Katsambas, A

2002-09-01

Topical application of isotretinoin and adapalene has proved effective in treating acne vulgaris. Both drugs demonstrate therapeutic advantages and less irritancy over tretinoin, the most widely used treatment for acne. They both act as retinoid agonists, but differ in their affinity profile for nuclear and cytosolic retinoic acid receptors. To compare the efficacy and tolerability of adapalene gel 0.1% and isotretinoin gel 0.05% in the treatment of acne vulgaris of the face, in a randomized open-label clinical trial. Eighty patients were enrolled and were instructed to apply adapalene gel 0.1% or isotretinoin gel 0.05% once daily over a 12-week treatment period. Efficacy determination included noninflammatory and inflammatory lesion counts by the investigator and global evaluation of improvement. Cutaneous tolerance was assessed by determining erythema, scaling and burning with pruritus. Adapalene and isotretinoin gels were highly effective in treating facial acne. Adapalene gel produced greater reductions in noninflammatory and inflammatory lesion counts than did isotretinoin gel, but differences between treatments were not statistically significant. Adapalene gel was significantly better tolerated than isotretinoin gel during the whole treatment period. The two gels studied demonstrated comparable efficacy. When adapalene and isotretinoin were compared, significantly lower skin irritation was noted with adapalene, indicating that adapalene may begin a new era of treatment with low-irritant retinoids.

Immune tolerance improves the efficacy of enzyme replacement therapy in canine mucopolysaccharidosis I

PubMed Central

Dickson, Patricia; Peinovich, Maryn; McEntee, Michael; Lester, Thomas; Le, Steven; Krieger, Aimee; Manuel, Hayden; Jabagat, Catherine; Passage, Merry; Kakkis, Emil D.

2008-01-01

Mucopolysaccharidoses (MPSs) are lysosomal storage diseases caused by a deficit in the enzymes needed for glycosaminoglycan (GAG) degradation. Enzyme replacement therapy with recombinant human α-l-iduronidase successfully reduces lysosomal storage in canines and humans with iduronidase-deficient MPS I, but therapy usually also induces antibodies specific for the recombinant enzyme that could reduce its efficacy. To understand the potential impact of α-l-iduronidase–specific antibodies, we studied whether inducing antigen-specific immune tolerance to iduronidase could improve the effectiveness of recombinant iduronidase treatment in canines. A total of 24 canines with MPS I were either tolerized to iduronidase or left nontolerant. All canines received i.v. recombinant iduronidase at the FDA-approved human dose or a higher dose for 9–44 weeks. Nontolerized canines developed iduronidase-specific antibodies that proportionally reduced in vitro iduronidase uptake. Immune-tolerized canines achieved increased tissue enzyme levels at either dose in most nonreticular tissues and a greater reduction in tissue GAG levels, lysosomal pathology, and urinary GAG excretion. Tolerized MPS I dogs treated with the higher dose received some further benefit in the reduction of GAGs in tissues, urine, and the heart valve. Therefore, immune tolerance to iduronidase improved the efficacy of enzyme replacement therapy with recombinant iduronidase in canine MPS I and could potentially improve outcomes in patients with MPS I and other lysosomal storage diseases. PMID:18654665

Effects, tolerance mechanisms and management of salt stress in grain legumes.

PubMed

Farooq, Muhammad; Gogoi, Nirmali; Hussain, Mubshar; Barthakur, Sharmistha; Paul, Sreyashi; Bharadwaj, Nandita; Migdadi, Hussein M; Alghamdi, Salem S; Siddique, Kadambot H M

2017-09-01

Salt stress is an ever-present threat to crop yields, especially in countries with irrigated agriculture. Efforts to improve salt tolerance in crop plants are vital for sustainable crop production on marginal lands to ensure future food supplies. Grain legumes are a fascinating group of plants due to their high grain protein contents and ability to fix biological nitrogen. However, the accumulation of excessive salts in soil and the use of saline groundwater are threatening legume production worldwide. Salt stress disturbs photosynthesis and hormonal regulation and causes nutritional imbalance, specific ion toxicity and osmotic effects in legumes to reduce grain yield and quality. Understanding the responses of grain legumes to salt stress and the associated tolerance mechanisms, as well as assessing management options, may help in the development of strategies to improve the performance of grain legumes under salt stress. In this manuscript, we discuss the effects, tolerance mechanisms and management of salt stress in grain legumes. The principal inferences of the review are: (i) salt stress reduces seed germination (by up to more than 50%) either by inhibiting water uptake and/or the toxic effect of ions in the embryo, (ii) salt stress reduces growth (by more than 70%), mineral uptake, and yield (by 12-100%) due to ion toxicity and reduced photosynthesis, (iii) apoplastic acidification is a good indicator of salt stress tolerance, (iv) tolerance to salt stress in grain legumes may develop through excretion and/or compartmentalization of toxic ions, increased antioxidant capacity, accumulation of compatible osmolytes, and/or hormonal regulation, (v) seed priming and nutrient management may improve salt tolerance in grain legumes, (vi) plant growth promoting rhizobacteria and arbuscular mycorrhizal fungi may help to improve salt tolerance due to better plant nutrient availability, and (vii) the integration of screening, innovative breeding, and the development of transgenics and crop management strategies may enhance salt tolerance and yield in grain legumes on salt-affected soils. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Randomized study comparing the efficacy and tolerance of a lipohydroxy acid shampoo to a ciclopiroxolamine shampoo in the treatment of scalp seborrheic dermatitis.

PubMed

Seite, Sophie; Rougier, André; Talarico, Sergio

2009-12-01

The success of a dandruff treatment depends not only on the ability of a shampoo to control dandruff, but also on patient compliance, which is closely linked to the cosmetic attributes of the product. The aim of this study was to compare efficacy, tolerance, and cosmetic properties of a LHA Shampoo [containing 0.1% lipohydroxy acid (LHA) and 1.3% salicylic acid] to a CPO shampoo [containing 1.5% ciclopiroxolamine (CPO), 3% salicylic acid, and 0.5% menthol] in subjects with seborrheic dermatitis (SD) of the scalp. One hundred subjects with mild to moderate scalp SD were randomized to receive either the LHA shampoo or the CPO shampoo every 2 days for 4 weeks. Efficacy and tolerance were evaluated at days 0, 14, and 28. The LHA and the CPO shampoo both decreased symptoms of scale, erythema, itching, cutaneous discomfort, and dryness from baseline to day 28. A higher percentage of patients showed improvement in the group treated with the LHA formulation than in the group treated with the CPO formulation, but the difference did not reach statistical significance. At day 28, the tolerance and the global efficacy of the LHA shampoo were significantly better (P = 0.03 and P = 0.01, respectively) than those of the CPO shampoo. Furthermore, the cosmetic acceptability was better or significantly better for all the endpoints evaluated for the LHA shampoo (P = 0.02 for cleaning, P = 0.04 for lathering). In conclusion, these results demonstrated that the lipohydroxy acid shampoo evaluated in this study is a more convenient, efficient, safe, and well-tolerated cosmetic treatment for mild-to-moderate seborrheic dermatitis of the scalp than a ciclopiroxolamine shampoo.

Standardized Mixed-Meal Tolerance and Arginine Stimulation Tests Provide Reproducible and Complementary Measures of β-Cell Function: Results From the Foundation for the National Institutes of Health Biomarkers Consortium Investigative Series

PubMed Central

Shankar, Sudha S.; Vella, Adrian; Raymond, Ralph H.; Staten, Myrlene A.; Calle, Roberto A.; Bergman, Richard N.; Cao, Charlie; Chen, Danny; Cobelli, Claudio; Dalla Man, Chiara; Deeg, Mark; Dong, Jennifer Q.; Lee, Douglas S.; Polidori, David; Robertson, R. Paul; Ruetten, Hartmut; Stefanovski, Darko; Vassileva, Maria T.; Weir, Gordon C.

2016-01-01

OBJECTIVE Standardized, reproducible, and feasible quantification of β-cell function (BCF) is necessary for the evaluation of interventions to improve insulin secretion and important for comparison across studies. We therefore characterized the responses to, and reproducibility of, standardized methods of in vivo BCF across different glucose tolerance states. RESEARCH DESIGN AND METHODS Participants classified as having normal glucose tolerance (NGT; n = 23), prediabetes (PDM; n = 17), and type 2 diabetes mellitus (T2DM; n = 22) underwent two standardized mixed-meal tolerance tests (MMTT) and two standardized arginine stimulation tests (AST) in a test-retest paradigm and one frequently sampled intravenous glucose tolerance test (FSIGT). RESULTS From the MMTT, insulin secretion in T2DM was >86% lower compared with NGT or PDM (P < 0.001). Insulin sensitivity (Si) decreased from NGT to PDM (∼50%) to T2DM (93% lower [P < 0.001]). In the AST, insulin secretory response to arginine at basal glucose and during hyperglycemia was lower in T2DM compared with NGT and PDM (>58%; all P < 0.001). FSIGT showed decreases in both insulin secretion and Si across populations (P < 0.001), although Si did not differ significantly between PDM and T2DM populations. Reproducibility was generally good for the MMTT, with intraclass correlation coefficients (ICCs) ranging from ∼0.3 to ∼0.8 depending on population and variable. Reproducibility for the AST was very good, with ICC values >0.8 across all variables and populations. CONCLUSIONS Standardized MMTT and AST provide reproducible and complementary measures of BCF with characteristics favorable for longitudinal interventional trials use. PMID:27407117

Standardized Mixed-Meal Tolerance and Arginine Stimulation Tests Provide Reproducible and Complementary Measures of β-Cell Function: Results From the Foundation for the National Institutes of Health Biomarkers Consortium Investigative Series.

PubMed

Shankar, Sudha S; Vella, Adrian; Raymond, Ralph H; Staten, Myrlene A; Calle, Roberto A; Bergman, Richard N; Cao, Charlie; Chen, Danny; Cobelli, Claudio; Dalla Man, Chiara; Deeg, Mark; Dong, Jennifer Q; Lee, Douglas S; Polidori, David; Robertson, R Paul; Ruetten, Hartmut; Stefanovski, Darko; Vassileva, Maria T; Weir, Gordon C; Fryburg, David A

2016-09-01

Standardized, reproducible, and feasible quantification of β-cell function (BCF) is necessary for the evaluation of interventions to improve insulin secretion and important for comparison across studies. We therefore characterized the responses to, and reproducibility of, standardized methods of in vivo BCF across different glucose tolerance states. Participants classified as having normal glucose tolerance (NGT; n = 23), prediabetes (PDM; n = 17), and type 2 diabetes mellitus (T2DM; n = 22) underwent two standardized mixed-meal tolerance tests (MMTT) and two standardized arginine stimulation tests (AST) in a test-retest paradigm and one frequently sampled intravenous glucose tolerance test (FSIGT). From the MMTT, insulin secretion in T2DM was >86% lower compared with NGT or PDM (P < 0.001). Insulin sensitivity (Si) decreased from NGT to PDM (∼50%) to T2DM (93% lower [P < 0.001]). In the AST, insulin secretory response to arginine at basal glucose and during hyperglycemia was lower in T2DM compared with NGT and PDM (>58%; all P < 0.001). FSIGT showed decreases in both insulin secretion and Si across populations (P < 0.001), although Si did not differ significantly between PDM and T2DM populations. Reproducibility was generally good for the MMTT, with intraclass correlation coefficients (ICCs) ranging from ∼0.3 to ∼0.8 depending on population and variable. Reproducibility for the AST was very good, with ICC values >0.8 across all variables and populations. Standardized MMTT and AST provide reproducible and complementary measures of BCF with characteristics favorable for longitudinal interventional trials use. © 2016 by the American Diabetes Association.

SU-F-T-271: Comparing IMRT QA Pass Rates Before and After MLC Calibration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mazza, A; Perrin, D; Fontenot, J

Purpose: To compare IMRT QA pass rates before and after an in-house MLC leaf calibration procedure. Methods: The MLC leaves and backup jaws on four Elekta linear accelerators with MLCi2 heads were calibrated using the EPID-based RIT Hancock Test as the means for evaluation. The MLCs were considered to be successfully calibrated when they could pass the Hancock Test with criteria of 1 mm jaw position tolerance, and 1 mm leaf position tolerance. IMRT QA results were collected pre- and postcalibration and analyzed using gamma analysis with 3%/3mm DTA criteria. AAPM TG-119 test plans were also compared pre- and post-calibration,more » at both 2%/2mm DTA and 3%/3mm DTA. Results: A weighted average was performed on the results for all four linear accelerators. The pre-calibration IMRT QA pass rate was 98.3 ± 0.1%, compared with the post-calibration pass rate of 98.5 ± 0.1%. The TG-119 test plan results showed more of an improvement, particularly at the 2%/2mm criteria. The averaged results were 89.1% pre and 96.1% post for the C-shape plan, 94.8% pre and 97.1% post for the multi-target plan, 98.6% pre and 99.7% post for the prostate plan, 94.7% pre and 94.8% post for the head/neck plan. Conclusion: The patient QA results did not show statistically significant improvement at the 3%/3mm DTA criteria after the MLC calibration procedure. However, the TG-119 test cases did show significant improvement at the 2%/2mm level.« less

Brazilian Morus nigra Attenuated Hyperglycemia, Dyslipidemia, and Prooxidant Status in Alloxan-Induced Diabetic Rats

PubMed Central

Júnior, Ivanildo I. da S.; Barbosa, Humberto de Moura; Carvalho, Débora C. R.; Barros, Ruideglan de Alencar; Albuquerque, Flávia Peixoto; da Silva, Dionísio Henrique Amaral; Souza, Grasielly R.; Souza, Nathália A. C.; Silva, Flaviane M. M.; Duarte, Glória I. B. P.; de Oliveira Júnior, Flávio Monteiro; Gomes, Dayane A.

2017-01-01

Morus nigra has been used popularly for several proposes, including diabetic. In an attempt to support medicinal value, the acute hypoglycemic, hypolipidemic, and antioxidant effects of the ethanolic extract of Morus nigra (EEMn 200 or 400 mg/kg b.w.) were evaluated in normal and alloxan-induced diabetic treated for 14 days. Serum biochemical and antioxidant analysis were performed at the end of experiment. Oral glucose tolerance test was performed at 10th and 15th days. Chromatographic analysis by HPLC-DAD of EEMn was performed. Insulin was used as positive control to glycemic metabolism as well as fenofibrate to lipid metabolism. EEMn (400 mg/kg/day) reduced fasting and postprandial glycaemia, improved oral glucose tolerance, and reduced lipolysis and proteolysis in diabetic rats. EEMn decreased the blood levels of total cholesterol and increased HDL level when compared to the diabetic control rats. At higher levels, EEMn reduced triglycerides and VLDL levels in diabetic rats. Also, EEMn reduced malondialdehyde and increased the reduced glutathione levels in liver of diabetic rats. Chromatographic analysis identified the presence of the flavonoids rutin, isoquercetin, and kaempferitrin. Acute EEMn treatment reduced hyperglycemia, improved oral glucose tolerance, and minimized dyslipidemia and oxidative stress leading to a reduction in atherogenic index in alloxan-induced diabetic rats. PMID:28567440

Wheat TaPUB1 modulates plant drought stress resistance by improving antioxidant capability.

PubMed

Zhang, Guangqiang; Zhang, Meng; Zhao, Zhongxian; Ren, Yuanqing; Li, Qinxue; Wang, Wei

2017-08-08

E3 ligases play significant roles in plant stress tolerance by targeting specific substrate proteins for post-translational modification. In a previous study, we cloned TaPUB1 from Triticum aestivum L., which encodes a U-box E3 ligase. Real-time polymerase chain reaction revealed that the gene was up-regulated under drought stress. To investigate the function of TaPUB1 in the response of plants to drought, we generated transgenic Nicotiana benthamiana (N. benthamiana) plants constitutively expressing TaPUB1 under the CaMV35S promoter. Compared to wild type (WT), the transgenic plants had higher germination and seedling survival rates as well as higher photosynthetic rate and water retention, suggesting that the overexpression of TaPUB1 enhanced the drought tolerance of the TaPUB1 overexpressing (OE) plants. Moreover, less accumulation of reactive oxygen species (ROS) and stronger antioxidant capacity were detected in the OE plants than in the WT plants. To characterize the mechanisms involved, methyl viologen (MV) was used to induce oxidative stress conditions and we identified the functions of this gene in the plant tolerance to oxidative stress. Our results suggest that TaPUB1 positively modulates plant drought stress resistance potential by improving their antioxidant capacity.

Lubiprostone plus PEG electrolytes versus placebo plus PEG electrolytes for outpatient colonoscopy preparation: a randomized, double-blind placebo-controlled trial.

PubMed

Sofi, Aijaz A; Nawras, Ali T; Pai, Chetan; Samuels, Qiana; Silverman, Ann L

2015-01-01

Bowel preparation using large volume of polyethylene glycol (PEG) solutions is often poorly tolerated. Therefore, there are ongoing efforts to develop an alternative bowel cleansing regimen that should be equally effective and better tolerated. The aim of this study was to assess the efficacy of lubiprostone (versus placebo) plus PEG as a bowel cleansing preparation for colonoscopy. Our study was a randomized, double-blind placebo-controlled design. Patients scheduled for screening colonoscopy were randomized 1:1 to lubiprostone (group 1) or placebo (group 2) plus 1 gallon of PEG. The primary endpoints were patient's tolerability and endoscopist's evaluation of the preparation quality. The secondary endpoint was to determine any reduction in the amount of PEG consumed in the lubiprostone group compared with the placebo group. One hundred twenty-three patients completed the study and were included in the analysis. There was no difference in overall cleanliness. The volume of PEG was similar in both the groups. The volume of PEG approached significance as a predictor of improved score for both the groups (P = 0.054). Lubiprostone plus PEG was similar to placebo plus PEG in colon cleansing and volume of PEG consumed. The volume of PEG consumed showed a trend toward improving the quality of the colon cleansing.

Deciphering endophyte behaviour: the link between endophyte biology and efficacious biological control agents.

PubMed

Card, Stuart; Johnson, Linda; Teasdale, Suliana; Caradus, John

2016-08-01

Endophytes associate with the majority of plant species found in natural and managed ecosystems. They are regarded as extremely important plant partners that provide improved stress tolerance to the host compared with plants that lack this symbiosis. Fossil records of endophytes date back more than 400 million years, implicating these microorganisms in host plant adaptation to habitat transitions. However, it is only recently that endophytes, and their bioactive products, have received meaningful attention from the scientific community. The benefits some endophytes can confer on their hosts include plant growth promotion and survival through the inhibition of pathogenic microorganisms and invertebrate pests, the removal of soil contaminants, improved tolerance of low fertility soils, and increased tolerance of extreme temperatures and low water availability. Endophytes are extremely diverse and can exhibit many different biological behaviours. Not all endophyte technologies have been successfully commercialised. Of interest in the development of the next generation of plant protection products is how much of this is due to the biology of the particular endophytic microorganism. In this review, we highlight selected case studies of endophytes and discuss their lifestyles and behavioural traits, and discuss how these factors contribute towards their effectiveness as biological control agents. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Efficacy and tolerability of fimasartan, a new angiotensin receptor blocker, compared with losartan (50/100 mg): a 12-week, phase III, multicenter, prospective, randomized, double-blind, parallel-group, dose escalation clinical trial with an optional 12-week extension phase in adult Korean patients with mild-to-moderate hypertension.

PubMed

Lee, Sang Eun; Kim, Yong-Jin; Lee, Hae-Young; Yang, Han-Mo; Park, Chang-Gyu; Kim, Jae-Joong; Kim, Soon-Kil; Rhee, Moo-Yong; Oh, Byung-Hee

2012-03-01

Angiotensin receptor blockers (ARBs) is an effective and well tolerated first-line antihypertensive drug. Fimasartan is a newly developed ARB that has not been compared with other ARBs with regard to its efficacy and tolerability. The goal of this study was to determine the noninferiority of fimasartan to losartan with regard to its efficacy and tolerability in adult Korean patients with mild-to-moderate hypertension. This was a randomized, multicenter, double-blind, parallel group, dose escalation, Phase III, noninferiority clinical trial. Patients aged 18 to 70 years with mild-to-moderate hypertension were randomized to receive either fimasartan 60/120 mg daily or losartan 50/100 mg daily with optional titration. Antihypertensive efficacy and tolerability were evaluated for 12 weeks. The primary end point was noninferiority of improvement in mean siDBP from baseline to week 12 for fimasartan compared with losartan. The incidence and severity of adverse events (AEs) and adverse drug reactions (ADRs) were evaluated to assess their tolerability. In addition, some patients whose blood pressure reached goal levels participated in a 24-week extension study for additional assessment of tolerability and efficacy. Five hundred six patients were randomly allocated to receive fimasartan (n = 256) or losartan (n = 250). There was no significant difference in baseline demographic characteristics between the 2 treatment groups (fimasartan-treated group-mean age, 53.96 [8.79] years; mean weight, 70.58 [11.73] kg; male, 68.02%; losartan-treated group-mean age, 53.58 [9.61] years; mean weight, 69.80 [11.08] kg; male, 70.17%). At week 12, siDBP was significantly decreased from baseline in both groups (-11.26 [7.53] mm Hg in the fimasartan group and -8.56 [7.72] mm Hg in the losartan group [P < 0.0001]). The between-group difference was 2.70 mm Hg (P = 0.0002), and the lower limit of the 2-sided 95% CI (1.27 mm Hg) was higher than the prespecified noninferiority margin (-2.5 mm Hg). The incidence of ADRs were 7.84% and 10.40% in the fimasartan and losartan groups, respectively (χ(2) test, P = 0.3181). The efficacy of fimasartan was maintained over 24 weeks, and its tolerability was comparable with losartan in the extension study. In this study with eligible adult Korean patients who had mild-to-moderate hypertension, the reduction of siDBP after 12 weeks of treatment with fimasartan 60/120 mg was noninferior to that of losartan 50/100 mg. By post hoc comparison, between-group differences in siDBP were significant in favor of fimasartan, suggesting superiority to losartan. There was no statistically significant difference in tolerability between the groups. This efficacy and tolerability were maintained throughout the additional 12-week extension study. Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

Adaptive evolution of the lager brewing yeast Saccharomyces pastorianus for improved growth under hyperosmotic conditions and its influence on fermentation performance.

PubMed

Ekberg, Jukka; Rautio, Jari; Mattinen, Laura; Vidgren, Virve; Londesborough, John; Gibson, Brian R

2013-05-01

An adaptive evolution method to obtain stable Saccharomyces pastorianus brewing yeast variants with improved fermentation capacity is described. The procedure involved selection for rapid growth resumption at high osmotic strength. It was applied to a lager strain and to a previously isolated ethanol-tolerant strain. Fermentation performance of strains was compared at 15 °P wort strength. A selected osmotolerant variant of the ethanol-tolerant strain showed significantly shorter fermentation time than the parent strain, producing 6.45% alcohol by volume beer in 4-5 days with mostly similar organoleptic properties to the original strain. Diacetyl and pentanedione contents were 50-75% and 3-methylbutyl acetate and 2-phenylethyl acetate 50% higher than with the original strain, leading to a small flavour change. The variant contained significantly less intracellular trehalose and glycogen than the parent. Transcriptional analysis of selected genes at 24 h revealed reduced transcription of hexose transport genes and increased transcription of the MALx1 and MALx2 genes, responsible for α-glucoside uptake and metabolism. It is suggested that an attenuated stress response contributes to the improved fermentation performance. Results show that sequential selection for both ethanol tolerance and rapid growth at high osmotic strength can provide strains with enhanced fermentation speed with acceptable product quality. © 2013 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Improving nutritional quality and fungal tolerance in soya bean and grass pea by expressing an oxalate decarboxylase.

PubMed

Kumar, Vinay; Chattopadhyay, Arnab; Ghosh, Sumit; Irfan, Mohammad; Chakraborty, Niranjan; Chakraborty, Subhra; Datta, Asis

2016-06-01

Soya bean (Glycine max) and grass pea (Lathyrus sativus) seeds are important sources of dietary proteins; however, they also contain antinutritional metabolite oxalic acid (OA). Excess dietary intake of OA leads to nephrolithiasis due to the formation of calcium oxalate crystals in kidneys. Besides, OA is also a known precursor of β-N-oxalyl-L-α,β-diaminopropionic acid (β-ODAP), a neurotoxin found in grass pea. Here, we report the reduction in OA level in soya bean (up to 73%) and grass pea (up to 75%) seeds by constitutive and/or seed-specific expression of an oxalate-degrading enzyme, oxalate decarboxylase (FvOXDC) of Flammulina velutipes. In addition, β-ODAP level of grass pea seeds was also reduced up to 73%. Reduced OA content was interrelated with the associated increase in seeds micronutrients such as calcium, iron and zinc. Moreover, constitutive expression of FvOXDC led to improved tolerance to the fungal pathogen Sclerotinia sclerotiorum that requires OA during host colonization. Importantly, FvOXDC-expressing soya bean and grass pea plants were similar to the wild type with respect to the morphology and photosynthetic rates, and seed protein pool remained unaltered as revealed by the comparative proteomic analysis. Taken together, these results demonstrated improved seed quality and tolerance to the fungal pathogen in two important legume crops, by the expression of an oxalate-degrading enzyme. © 2016 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

Differential Responses of Polyamines and Antioxidants to Drought in a Centipedegrass Mutant in Comparison to Its Wild Type Plants

PubMed Central

Liu, Mingxi; Chen, Jingjing; Guo, Zhenfei; Lu, Shaoyun

2017-01-01

Centipedegrass (Eremochloa ophiuroides [Munro] Hack.) is an important warm-season turfgrass species with low turf maintenance requirements. However, our knowledge on physiological adaptation of centipedegrass to drought stress is limited. Physiological responses to drought in a gamma-ray-induced mutant 22-1 as compared with two wild type (WT) lines were analyzed for understanding of drought tolerance mechanism of centipedegrass. The mutant showed an elevated drought tolerance with higher levels of relative water content, net photosynthetic rate (A) and stomatal conductance (gs) and lower levels of ion leakage and malondialdehyde (MDA) under drought stress as compared with WT plants. A showed significant correlation with gs and MDA. Higher levels of antioxidant enzymes activities, non-enzyme antioxidants, and polyamines including putrescine (Put), spermidine (Spd), and spermine (Spm) were maintained in 22-1 than in WT plants. Superoxide dismutase (SOD), catalase (CAT), ascorbate-peroxidase (APX), and glutathione reductase (GR) activities and ascorbic acid (AsA) content were significantly correlated with both Put and Spd levels, and reduced glutathione level was correlated with Put during drought stress. Exogenous application of Put, Spd, and Spm increased drought tolerance and activities of SOD, CAT, APX, and GR in WT plants. The results suggest that higher levels of polyamines and antioxidant defense system are associated with the elevated drought tolerance in 22-1, which may improve protection on photosynthesis against drought induced oxidative damage. PMID:28559909

Comparison of efficacies of a dipeptidyl peptidase IV inhibitor and alpha-glucosidase inhibitors in oral carbohydrate and meal tolerance tests and the effects of their combination in mice.

PubMed

Yamazaki, Kazuto; Inoue, Takashi; Yasuda, Nobuyuki; Sato, Yoshiaki; Nagakura, Tadashi; Takenaka, Osamu; Clark, Richard; Saeki, Takao; Tanaka, Isao

2007-05-01

E3024 (3-but-2-ynyl-5-methyl-2-piperazin-1-yl-3,5-dihydro-4H-imidazo[4,5-d]pyridazin-4-one tosylate) is a dipeptidyl peptidase IV (DPP-IV) inhibitor. Since the target of both DPP-IV inhibitors and alpha-glucosidase inhibitors is the lowering of postprandial hyperglycemia, we compared antihyperglycemic effects for E3024 and alpha-glucosidase inhibitors in various oral carbohydrate and meal tolerance tests using normal mice. In addition, we investigated the combination effects of E3024 and voglibose on blood glucose levels in a meal tolerance test using mice fed a high-fat diet. ER-235516-15 (the trifluoroacetate salt form of E3024, 1 mg/kg) lowered glucose excursions consistently, regardless of the kind of carbohydrate loaded. However, the efficacy of acarbose (10 mg/kg) and of voglibose (0.1 mg/kg) varied with the type of carbohydrate administered. The combination of E3024 (3 mg/kg) and voglibose (0.3 mg/kg) improved glucose tolerance additively, with the highest plasma active glucagon-like peptide-1 levels. This study shows that compared to alpha-glucosidase inhibitors, DPP-IV inhibitors may have more consistent efficacy to reduce postprandial hyperglycemia, independent of the types of carbohydrate contained in a meal, and that the combination of a DPP-IV inhibitor and an alpha-glucosidase inhibitor is expected to be a promising option for lowering postprandial hyperglycemia.

Bioprospecting for Genes that Confer Biofuel Tolerance to Escherichia Coli Using a Genomic Library Approach

NASA Astrophysics Data System (ADS)

Tomko, Timothy

Microorganisms are capable of producing advanced biofuels that can be used as 'drop-in' alternatives to conventional liquid fuels. However, vital physiological processes and membrane properties are often disrupted by the presence of biofuel and limit the production yields. In order to make microbial biofuels a competitive fuel source, finding mechanisms for improving resistance to the toxic effects of biofuel production is vital. This investigation aims to identify resistance mechanisms from microorganisms that have evolved to withstand hydrocarbon-rich environments, such as those that thrive near natural oil seeps and in oil-polluted waters. First, using genomic DNA from Marinobacter aquaeolei, we constructed a transgenic library that we expressed in Escherichia coli. We exposed cells to inhibitory levels of pinene, a monoterpene that can serve as a jet fuel precursor with chemical properties similar to existing tactical fuels. Using a sequential strategy of a fosmid library followed by a plasmid library, we were able to isolate a region of DNA from the M. aquaeolei genome that conferred pinene tolerance when expressed in E. coli. We determined that a single gene, yceI, was responsible for the tolerance improvements. Overexpression of this gene placed no additional burden on the host. We also tested tolerance to other monoterpenes and showed that yceI selectively improves tolerance. Additionally, we used genomic DNA from Pseudomonas putida KT2440, which has innate solvent-tolerance properties, to create transgenic libraries in an E. coli host. We exposed cells containing the library to pinene, selecting for genes that improved tolerance. Importantly, we found that expressing the sigma factor RpoD from P. putida greatly expanded the diversity of tolerance genes recovered. With low expression of rpoDP. putida, we isolated a single pinene tolerance gene; with increased expression of the sigma factor our selection experiments returned multiple distinct tolerance mechanisms, including some that have been previously documented and also new mechanisms. Interestingly, high levels of rpoDP. putida, induction resulted in decreased diversity. We found that the tolerance levels provided by some genes are highly sensitive to the level of induction of rpoD P. putida,, while others provide tolerance across a wide range of rpoDP. putida, levels. This method for unlocking diversity in tolerance screening using heterologous sigma factor expression was applicable to both plasmid and fosmid-based transgenic libraries. These results suggest that by controlling the expression of appropriate heterologous sigma factors, we can greatly increase the searchable genomic space within transgenic libraries. This dissertation describes a method of effectively screening genomic DNA from multiple organisms for genes to mitigate biofuel stress and shows how tolerance genes can improve bacterial growth in the presence of toxic biofuel compounds. These identified genes can be targeted in future studies as candidates for use in biofuel production strains to increase biofuel yields.

Identification of Rice Genes Associated With Enhanced Cold Tolerance by Comparative Transcriptome Analysis With Two Transgenic Rice Plants Overexpressing DaCBF4 or DaCBF7, Isolated From Antarctic Flowering Plant Deschampsia antarctica

PubMed Central

Byun, Mi Young; Cui, Li Hua; Lee, Jungeun; Park, Hyun; Lee, Andosung; Kim, Woo Taek; Lee, Hyoungseok

2018-01-01

Few plant species can survive in Antarctica, the harshest environment for living organisms. Deschampsia antarctica is the only natural grass species to have adapted to and colonized the maritime Antarctic. To investigate the molecular mechanism of the Antarctic adaptation of this plant, we identified and characterized D. antarctica C-repeat binding factor 4 (DaCBF4), which belongs to monocot CBF group IV. The transcript level of DaCBF4 in D. antarctica was markedly increased by cold and dehydration stress. To assess the roles of DaCBF4 in plants, we generated a DaCBF4-overexpressing transgenic rice plant (Ubi:DaCBF4) and analyzed its abiotic stress response phenotype. Ubi:DaCBF4 displayed enhanced tolerance to cold stress without growth retardation under any condition compared to wild-type plants. Because the cold-specific phenotype of Ubi:DaCBF4 was similar to that of Ubi:DaCBF7 (Byun et al., 2015), we screened for the genes responsible for the improved cold tolerance in rice by selecting differentially regulated genes in both transgenic rice lines. By comparative transcriptome analysis using RNA-seq, we identified 9 and 15 genes under normal and cold-stress conditions, respectively, as putative downstream targets of the two D. antarctica CBFs. Overall, our results suggest that Antarctic hairgrass DaCBF4 mediates the cold-stress response of transgenic rice plants by adjusting the expression levels of a set of stress-responsive genes in transgenic rice plants. Moreover, selected downstream target genes will be useful for genetic engineering to enhance the cold tolerance of cereal plants, including rice. PMID:29774046

Mouse handling limits the impact of stress on metabolic endpoints.

PubMed

Ghosal, Sriparna; Nunley, Amanda; Mahbod, Parinaz; Lewis, Alfor G; Smith, Eric P; Tong, Jenny; D'Alessio, David A; Herman, James P

2015-10-15

Studies focused on end-points that are confounded by stress are best performed under minimally stressful conditions. The objective of this study was to demonstrate the impact of handling designed to reduce animal stress on measurements of glucose tolerance. A cohort of mice (CD1.C57BL/6) naïve to any specific handling was subjected to either a previously described "cup" handling method, or a "tail-picked" method in which the animals were picked up by the tail (as is common for metabolic studies). Following training, an elevated plus maze (EPM) test was performed followed by measurement of blood glucose and plasma corticosterone. A second cohort (CD1.C57BL/6) was rendered obese by exposure to a high fat diet, handled with either the tail-picked or cup method and subjected to an intraperitoneal glucose tolerance test. A third cohort of C57BL/6 mice was exposed to a cup regimen that included a component of massage and was subjected to tests of anxiety-like behavior, glucose homeostasis, and corticosterone secretion. We found that the cup mice showed reduced anxiety-like behaviors in the EPM coupled with a reduction in blood glucose levels compared to mice handled by the tail-picked method. Additionally, cup mice on the high fat diet exhibited improved glucose tolerance compared to tail-picked controls. Finally, we found that the cup/massage group showed lower glucose levels following an overnight fast, and decreased anxiety-like behaviors associated with lower stress-induced plasma corticosterone concentration compared to tail-picked controls. These data demonstrate that application of handling methods that reduce anxiety-like behaviors in mice mitigates the confounding contribution of stress to interpretation of metabolic endpoints (such as glucose tolerance). Copyright © 2015 Elsevier Inc. All rights reserved.

Mouse Handling Limits the Impact of Stress on Metabolic Endpoints

PubMed Central

Ghosal, Sriparna; Nunley, Amanda; Mahbod, Parinaz; Lewis, Alfor G.; Smith, Eric P.; Tong, Jenny; D’Alessio, David A.; Herman, James P.

2015-01-01

Studies focused on end-points that are confounded by stress are best performed under minimally stressful conditions. The objective of this study was to demonstrate the impact of handling designed to reduce animal stress on measurements of glucose tolerance. A cohort of mice (CD1.C57BL/6) naïve to any specific handling were subjected to either a previously described “cup” handling method, or a “tail-picked” method in which the animals were picked up by the tail (as is common for metabolic studies). Following training, an elevated plus maze (EPM) test was performed followed by measurement of blood glucose and plasma corticosterone. A second cohort (CD1.C57BL/6) was rendered obese by exposure to a high fat diet, handled with either the tail-picked or cup method and subjected to an intraperitoneal glucose tolerance test. A third cohort of C57BL/6 mice was exposed to a cup regimen that included a component of massage and was subjected to tests of anxiety-like behavior, glucose homeostasis, and corticosterone secretion. We found that the cup mice showed reduced anxiety-like behaviors in the EPM coupled with a reduction in blood glucose levels compared to mice handled by the tail-picked method. Additionally, cup mice on the high fat diet exhibited improved glucose tolerance compared to tail-picked controls. Finally, we found that the cup/massage group showed lower glucose levels following an overnight fast, and decreased anxiety-like behaviors associated with lower stress-induced plasma corticosterone concentration compared to tail-picked controls. These data demonstrate that application of handling methods that reduce anxiety-like behaviors in mice mitigates the confounding contribution of stress to interpretation of metabolic endpoints (such as glucose tolerance). PMID:26079207

Identification of Rice Genes Associated With Enhanced Cold Tolerance by Comparative Transcriptome Analysis With Two Transgenic Rice Plants Overexpressing DaCBF4 or DaCBF7, Isolated From Antarctic Flowering Plant Deschampsia antarctica.

PubMed

Byun, Mi Young; Cui, Li Hua; Lee, Jungeun; Park, Hyun; Lee, Andosung; Kim, Woo Taek; Lee, Hyoungseok

2018-01-01

Few plant species can survive in Antarctica, the harshest environment for living organisms. Deschampsia antarctica is the only natural grass species to have adapted to and colonized the maritime Antarctic. To investigate the molecular mechanism of the Antarctic adaptation of this plant, we identified and characterized D. antarctica C-repeat binding factor 4 ( DaCBF4 ), which belongs to monocot CBF group IV. The transcript level of DaCBF4 in D. antarctica was markedly increased by cold and dehydration stress. To assess the roles of DaCBF4 in plants, we generated a DaCBF4 -overexpressing transgenic rice plant ( Ubi:DaCBF4 ) and analyzed its abiotic stress response phenotype. Ubi:DaCBF4 displayed enhanced tolerance to cold stress without growth retardation under any condition compared to wild-type plants. Because the cold-specific phenotype of Ubi:DaCBF4 was similar to that of Ubi:DaCBF7 (Byun et al., 2015), we screened for the genes responsible for the improved cold tolerance in rice by selecting differentially regulated genes in both transgenic rice lines. By comparative transcriptome analysis using RNA-seq, we identified 9 and 15 genes under normal and cold-stress conditions, respectively, as putative downstream targets of the two D. antarctica CBFs. Overall, our results suggest that Antarctic hairgrass DaCBF4 mediates the cold-stress response of transgenic rice plants by adjusting the expression levels of a set of stress-responsive genes in transgenic rice plants. Moreover, selected downstream target genes will be useful for genetic engineering to enhance the cold tolerance of cereal plants, including rice.

Introgression of a 4D chromosomal fragment into durum wheat confers aluminium tolerance

PubMed Central

Han, Chang; Ryan, Peter R.; Yan, ZeHong; Delhaize, Emmanuel

2014-01-01

Background and Aim Aluminium (Al3+) inhibits root growth of sensitive plant species and is a key factor that limits durum wheat (Triticum turgidum) production on acid soils. The aim of this study was to enhance the Al3+ tolerance of an elite durum cultivar by introgression of a chromosomal fragment from hexaploid wheat (Triticum aestivum) that possesses an Al3+ tolerance gene. Methods A 4D(4B) substitution line of durum wheat ‘Langdon’ was backcrossed to ‘Jandaroi’, a current semi-dwarf Australian durum. In the second backcross, using ‘Jandaroi’ as the recurrent parent, a seedling was identified where TaALMT1 on chromosome 4D was recombined with the Rht-B1b locus on chromosome 4B to yield an Al3+-tolerant seedling with a semi-dwarf habit. This seedling was used in a third backcross to generate homozygous sister lines with contrasting Al3+ tolerances. The backcrossed lines were characterized and compared with selected cultivars of hexaploid wheat for their Al3+ and Na+ tolerances in hydroponic culture as well as in short-term experiments to assess their growth on acid soil. Key Results Analysis of sister lines derived from the third backcross showed that the 4D chromosomal fragment substantially enhanced Al3+ tolerance. The ability to exclude Na+ from leaves was also enhanced, indicating that the chromosomal fragment possessed the Kna1 salt tolerance locus. Although Al3+ tolerance of seminal roots was enhanced in acid soil, the development of fine roots was not as robust as found in Al3+-tolerant lines of hexaploid wheat. Analysis of plant characteristics in the absence of Al3+ toxicity showed that the introgressed fragment did not affect total grain yield but reduced the weight of individual grains. Conclusions The results show that it is possible to increase substantially the Al3+ tolerance of an elite durum wheat cultivar by introgression of a 4D chromosomal fragment. Further improvements are possible, such as introducing additional genes to enhance the Al3+ tolerance of fine roots and by eliminating the locus on the chromosomal fragment responsible for smaller grain weights. PMID:24737716

Enhanced Drought Stress Tolerance by the Arbuscular Mycorrhizal Symbiosis in a Drought-Sensitive Maize Cultivar Is Related to a Broader and Differential Regulation of Host Plant Aquaporins than in a Drought-Tolerant Cultivar

PubMed Central

Quiroga, Gabriela; Erice, Gorka; Aroca, Ricardo; Chaumont, François; Ruiz-Lozano, Juan M.

2017-01-01

The arbuscular mycorrhizal (AM) symbiosis has been shown to improve maize tolerance to different drought stress scenarios by regulating a wide range of host plants aquaporins. The objective of this study was to highlight the differences in aquaporin regulation by comparing the effects of the AM symbiosis on root aquaporin gene expression and plant physiology in two maize cultivars with contrasting drought sensitivity. This information would help to identify key aquaporin genes involved in the enhanced drought tolerance by the AM symbiosis. Results showed that when plants were subjected to drought stress the AM symbiosis induced a higher improvement of physiological parameters in drought-sensitive plants than in drought-tolerant plants. These include efficiency of photosystem II, membrane stability, accumulation of soluble sugars and plant biomass production. Thus, drought-sensitive plants obtained higher physiological benefit from the AM symbiosis. In addition, the genes ZmPIP1;1, ZmPIP1;3, ZmPIP1;4, ZmPIP1;6, ZmPIP2;2, ZmPIP2;4, ZmTIP1;1, and ZmTIP2;3 were down-regulated by the AM symbiosis in the drought-sensitive cultivar and only ZmTIP4;1 was up-regulated. In contrast, in the drought-tolerant cultivar only three of the studied aquaporin genes (ZmPIP1;6, ZmPIP2;2, and ZmTIP4;1) were regulated by the AM symbiosis, resulting induced. Results in the drought-sensitive cultivar are in line with the hypothesis that down-regulation of aquaporins under water deprivation could be a way to minimize water loss, and the AM symbiosis could be helping the plant in this regulation. Indeed, during drought stress episodes, water conservation is critical for plant survival and productivity, and is achieved by an efficient uptake and stringently regulated water loss, in which aquaporins participate. Moreover, the broader and contrasting regulation of these aquaporins by the AM symbiosis in the drought-sensitive than the drought-tolerant cultivar suggests a role of these aquaporins in water homeostasis or in the transport of other solutes of physiological importance in both cultivars under drought stress conditions, which may be important for the AM-induced tolerance to drought stress. PMID:28674550

UAV remote sensing for phenotyping drought tolerance in peanuts

NASA Astrophysics Data System (ADS)

Balota, Maria; Oakes, Joseph

2017-05-01

Farmers can benefit from growing drought tolerant peanut (Arachis hypogaea L.) cultivars with improved yield when rainfall is sporadic. In the Virginia-Carolina (VC) region, drought is magnified by hot summers and usually occurs in July and Aug when pod and seed growth are intense. At these growth stages, weekly supply of 50 to 75 mm of water is needed to ensure profitability. Irrigation can supplement crop water needs, but only 10% of the peanut farms are irrigated. In this frame, drought tolerant varieties can be profitable, but breeding for cultivars with improved drought tolerance requires fast yet accurate phenotyping. Our objective was to evaluate the potential of UAV remote sensing technologies for drought tolerance selection in peanut. In this study, we examined the effect of drought on leaf wilting, pod yield, grading characteristics, and crop value of 23 peanut cultivars (Virginia, Runner, and Valencia type). These varieties were arranged in a factorial design, with four replications drought stressed and two replications well-watered. Drought was imposed by covering the drought stressed plots with rainout shelters on July 19; they remained covered until August 29 and only received 38 mm irrigation in mid Aug. The well-watered plots continued to receive rain and supplemental irrigation as needed. During this time, Canopy Temperature Depression (CT) and Normalized Differential Vegetative Index (NDVI) were collected from the ground on all plots at weekly intervals. After the shelters were removed, these measurements were collected daily for approximately 2 weeks. At the same time, Red-Green-Blue (RGB), near-infrared (NIR), and infrared (IR) images taken from an UAV platform were also collected. Vegetation indices derived from the ground and aerial data were compared with leaf wilting, pod yield and crop value. Wilting, which is a common water stress symptom, was best estimated by NDVI and RGB, and least by CT; but CT was best in estimating yield, SMK and crop value in particular when taken on the ground at 15 days water stress imposition. Interestingly, CT predicted well plant wilting even before it occurred, i.e., correlation coefficients were negative and over 0.750 when CT was measured on July 19 and 20 even though wilting was visible only after two weeks. The data, yet preliminary, show promising potential for remote sensing technologies, at the ground and aerial, for peanut variety selection for improved drought tolerance.

Improved ethanol production at high temperature by consolidated bioprocessing using Saccharomyces cerevisiae strain engineered with artificial zinc finger protein.

PubMed

Khatun, M Mahfuza; Yu, Xinshui; Kondo, Akihiko; Bai, Fengwu; Zhao, Xinqing

2017-12-01

In this work, the consolidated bioprocessing (CBP) yeast Saccharomyces cerevisiae MNII/cocδBEC3 was transformed by an artificial zinc finger protein (AZFP) library to improve its thermal tolerance, and the strain MNII-AZFP with superior growth at 42°C was selected. Improved degradation of acid swollen cellulose by 45.9% led to an increase in ethanol production, when compared to the control strain. Moreover, the fermentation of Jerusalem artichoke stalk (JAS) by MNII-AZFP was shortened by 12h at 42°C with a concomitant improvement in ethanol production. Comparative transcriptomics analysis suggested that the AZFP in the mutant exerted beneficial effect by modulating the expression of multiple functional genes. These results provide a feasible strategy for efficient ethanol production from JAS and other cellulosic biomass through CBP based-fermentation at elevated temperatures. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of eicosapentaenoic acid ethyl ester v. oleic acid-rich safflower oil on insulin resistance in type 2 diabetic model rats with hypertriacylglycerolaemia.

PubMed

Minami, Asako; Ishimura, Noriko; Sakamoto, Sadaichi; Takishita, Eiko; Mawatari, Kazuaki; Okada, Kazuko; Nakaya, Yutaka

2002-02-01

The purpose of the present study was to test whether hyperlipidaemia and insulin resistance in type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats can be improved by dietary supplementation with purified eicosapentaenoic acid (EPA) or oleic acid (OA). Male OLETF rats were fed powdered chow (510 g fat/kg) alone (n 8) or chow supplemented with 10 g EPA- (n 8) or OA- (n 8) rich oil/kg per d from 5 weeks until 30 weeks of age. An oral glucose tolerance test and hyperinsulinaemic euglycaemic clamp was performed at 25 and 30 weeks of age. EPA supplementation resulted in significantly (P<0.05) reduced plasma lipids, hepatic triacylglycerols, and abdominal fat deposits, and more efficient in vivo glucose disposal compared with OA supplementation and no supplementation. OA supplementation was associated with significantly increased insulin response to oral glucose compared with EPA supplementation and no supplementation. Inverse correlation was noted between glucose uptake and plasma triacylglycerol levels (r -086, P<0.001) and abdominal fat volume (r -0.80, P<0.001). The result of oral glucose tolerance test study showed that the rats fed EPA tended to improve glucose intolerance, although this was not statistically significant. Levels of plasma insulin at 60 min after glucose was significantly increased in rats fed OA compared with the other two groups. The results indicate that long-term feeding of EPA might be effective in preventing insulin resistance in diabetes-prone rats, at least in part, due to improving hypertriacylglycerolaemia.

Ectopic Expression of JcWRKY Transcription Factor Confers Salinity Tolerance via Salicylic Acid Signaling.

PubMed

Agarwal, Parinita; Dabi, Mitali; Sapara, Komal K; Joshi, Priyanka S; Agarwal, Pradeep K

2016-01-01

Plants, being sessile, have developed intricate signaling network to specifically respond to the diverse environmental stress. The plant-specific WRKY TFs form one of the largest TF family and are involved in diverse plant processes, involving growth, development and stress signaling through auto and cross regulation with different genes and TFs. Here, we report the functional characterization of a salicylic acid -inducible JcWRKY TF. The JcWRKY overexpression confers salinity tolerance in transgenic tobacco, as was evident by increased chlorophyll content and seed germination potential. The transgenic plants showed increased soluble sugar, membrane stability, reduced electrolyte leakage and generation of reactive oxygen species (H 2 O 2 and [Formula: see text]) as compared to the wild type. Furthermore, the low SA treatment along with salinity improved the tolerance potential of the transgenics by maintaining ROS homeostasis and high K + /Na + ratio. The transcript expression of SA biosynthetic gene ICS1 and antioxidative enzymes ( CAT and SOD ) showed upregulation during stress. Thus, the present study reflects that JcWRKY is working in co-ordination with SA signaling to orchestrate the different biochemical and molecular pathways to maneuvre salt stress tolerance of the transgenic plants.

Glossopharyngeal Nerve Block versus Lidocaine Spray to Improve Tolerance in Upper Gastrointestinal Endoscopy.

PubMed

Ortega Ramírez, Moisés; Linares Segovia, Benigno; García Cuevas, Marco Antonio; Sánchez Romero, Jorge Luis; Botello Buenrostro, Illich; Amador Licona, Norma; Guízar Mendoza, Juan Manuel; Guerrero Romero, Jesús Francisco; Vázquez Zárate, Víctor Manuel

2013-01-01

Aim of the Study. To compare the effect of glossopharyngeal nerve block with topical anesthesia on the tolerance of patients to upper gastrointestinal endoscopy. Methods. We performed a clinical trial in one hundred patients undergoing upper gastrointestinal endoscopy. Subjects were randomly assigned to one of the following two groups: (1) treatment with bilateral glossopharyngeal nerve block (GFNB) and intravenous midazolam or (2) treatment with topical anesthetic (TASS) and intravenous midazolam. We evaluated sedation, tolerance to the procedure, hemodynamic stability, and adverse symptoms. Results. We studied 46 men and 54 women, from 17 to 78 years of age. The procedure was reported without discomfort in 48 patients (88%) in the GFNB group and 32 (64%) in the TAAS group; 6 patients (12%) in GFNB group and 18 (36%) in TAAS group reported the procedure as little discomfort (χ (2) = 3.95, P = 0.04). There was no difference in frequency of nausea (4% in both groups) and retching, 4% versus 8% for GFNB and TASS group, respectively (P = 0.55). Conclusions. The use of glossopharyngeal nerve block provides greater comfort and tolerance to the patient undergoing upper gastrointestinal endoscopy. It also reduces the need for sedation.

Glossopharyngeal Nerve Block versus Lidocaine Spray to Improve Tolerance in Upper Gastrointestinal Endoscopy

PubMed Central

Ortega Ramírez, Moisés; Linares Segovia, Benigno; García Cuevas, Marco Antonio; Sánchez Romero, Jorge Luis; Botello Buenrostro, Illich; Amador Licona, Norma; Guízar Mendoza, Juan Manuel; Guerrero Romero, Jesús Francisco; Vázquez Zárate, Víctor Manuel

2013-01-01

Aim of the Study. To compare the effect of glossopharyngeal nerve block with topical anesthesia on the tolerance of patients to upper gastrointestinal endoscopy. Methods. We performed a clinical trial in one hundred patients undergoing upper gastrointestinal endoscopy. Subjects were randomly assigned to one of the following two groups: (1) treatment with bilateral glossopharyngeal nerve block (GFNB) and intravenous midazolam or (2) treatment with topical anesthetic (TASS) and intravenous midazolam. We evaluated sedation, tolerance to the procedure, hemodynamic stability, and adverse symptoms. Results. We studied 46 men and 54 women, from 17 to 78 years of age. The procedure was reported without discomfort in 48 patients (88%) in the GFNB group and 32 (64%) in the TAAS group; 6 patients (12%) in GFNB group and 18 (36%) in TAAS group reported the procedure as little discomfort (χ 2 = 3.95, P = 0.04). There was no difference in frequency of nausea (4% in both groups) and retching, 4% versus 8% for GFNB and TASS group, respectively (P = 0.55). Conclusions. The use of glossopharyngeal nerve block provides greater comfort and tolerance to the patient undergoing upper gastrointestinal endoscopy. It also reduces the need for sedation. PMID:23533386

Fault-Tolerant Algorithms for Connectivity Restoration in Wireless Sensor Networks.

PubMed

Zeng, Yali; Xu, Li; Chen, Zhide

2015-12-22

As wireless sensor network (WSN) is often deployed in a hostile environment, nodes in the networks are prone to large-scale failures, resulting in the network not working normally. In this case, an effective restoration scheme is needed to restore the faulty network timely. Most of existing restoration schemes consider more about the number of deployed nodes or fault tolerance alone, but fail to take into account the fact that network coverage and topology quality are also important to a network. To address this issue, we present two algorithms named Full 2-Connectivity Restoration Algorithm (F2CRA) and Partial 3-Connectivity Restoration Algorithm (P3CRA), which restore a faulty WSN in different aspects. F2CRA constructs the fan-shaped topology structure to reduce the number of deployed nodes, while P3CRA constructs the dual-ring topology structure to improve the fault tolerance of the network. F2CRA is suitable when the restoration cost is given the priority, and P3CRA is suitable when the network quality is considered first. Compared with other algorithms, these two algorithms ensure that the network has stronger fault-tolerant function, larger coverage area and better balanced load after the restoration.

The Design and Semi-Physical Simulation Test of Fault-Tolerant Controller for Aero Engine

NASA Astrophysics Data System (ADS)

Liu, Yuan; Zhang, Xin; Zhang, Tianhong

2017-11-01

A new fault-tolerant control method for aero engine is proposed, which can accurately diagnose the sensor fault by Kalman filter banks and reconstruct the signal by real-time on-board adaptive model combing with a simplified real-time model and an improved Kalman filter. In order to verify the feasibility of the method proposed, a semi-physical simulation experiment has been carried out. Besides the real I/O interfaces, controller hardware and the virtual plant model, semi-physical simulation system also contains real fuel system. Compared with the hardware-in-the-loop (HIL) simulation, semi-physical simulation system has a higher degree of confidence. In order to meet the needs of semi-physical simulation, a rapid prototyping controller with fault-tolerant control ability based on NI CompactRIO platform is designed and verified on the semi-physical simulation test platform. The result shows that the controller can realize the aero engine control safely and reliably with little influence on controller performance in the event of fault on sensor.

Antigen-specific tolerance inhibits autoimmune uveitis in pre-sensitized animals by deletion and CD4+CD25+ T-regulatory cells.

PubMed

Matta, Bharati; Jha, Purushottam; Bora, Puran S; Bora, Nalini S

2010-02-01

The objective of this study was to inhibit experimental autoimmune anterior uveitis (EAAU) by establishing antigen-specific immune tolerance in animals pre-sensitized with melanin-associated antigen (MAA). Intravenous administration of MAA on days 6, 7, 8 and 9 post-immunization induced tolerance and inhibited EAAU in all Lewis rats. The number of cells (total T cells, CD4(+) T cells and CD8(+) T cells) undergoing apoptosis dramatically increased in the popliteal lymph nodes (LNs) of the tolerized animals compared with non-tolerized animals. In addition, Fas ligand (FasL), TNF receptor 1 (TNFR1) and caspase-8 were upregulated in tolerized rats. Proliferation of total lymphocytes, CD4(+)T cells and CD8(+) T cells (harvested from the popliteal LNs) in response to antigenic stimulation was drastically reduced in the state of tolerance compared with the cells from non-tolerized animals. The level of interferon (IFN)-gamma and IL-2 decreased, whereas TGF-beta2 was elevated in the state of tolerance. Furthermore, the number of CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs) increased in the popliteal LNs of tolerized animals compared with non-tolerized animals. In conclusion, our results suggest that deletion of antigen-specific T cells by apoptosis and active suppression mediated by Tregs has an important role in the induction of antigen specific immune tolerance in animals with an established immune response against MAA.

2’-Behenoyl-Paclitaxel Conjugate Containing Lipid Nanoparticles for the Treatment of Metastatic Breast Cancer

PubMed Central

Ma, Ping; Benhabbour, S. Rahima; Feng, Lan; Mumper, Russell J

2012-01-01

The aim of these studies was to develop a novel 2’-behenoyl-paclitaxel (C22-PX) conjugate nanoparticle (NP) formulation for the treatment of metastatic breast cancer. A lipophilic paclitaxel derivative C22-PX was synthesized and incorporated into lipid-based NPs. Free C22-PX and its NP formulation were evaluated in a series of in-vitro and in-vivo studies. The results demonstrated that C22-PX NPs were much better tolerated and had significantly higher plasma and tumor AUCs compared to Taxol at the maximum tolerated dose (MTD) in a subcutaneous 4T1 mouse mammary carcinoma model. These benefits resulted in significantly improved antitumor efficacy with the NP-based formulation. PMID:22902506

Toll-Like Receptor 4 Stimulation before or after Streptococcus pneumoniae Induced Sepsis Improves Survival and Is Dependent on T-Cells

PubMed Central

Martin, Edward N.; Scheld, W. Michael

2014-01-01

Introduction Endotoxin tolerance improves outcomes from gram negative sepsis but the underlying mechanism is not known. We determined if endotoxin tolerance before or after pneumococcal sepsis improved survival and the role of lymphocytes in this protection. Methods Mice received lipopolysaccharide (LPS) or vehicle before or after a lethal dose of Streptococcus pneumoniae. Survival, quantitative bacteriology, liver function, and cytokine concentrations were measured. We confirmed the necessity of Toll-like receptor 4 (TLR4) for endotoxin tolerance using C3H/HeN (TLR4 replete) and C3H/HeJ (TLR4 deficient) mice. The role of complement was investigated through A/J mice deficient in C5 complement. CBA/CaHN-Btkxid//J mice with dysfunctional B cells and Rag-1 knockout (KO) mice deficient in T and B cells delineated the role of lymphocytes. Results Endotoxin tolerance improved survival from pneumococcal sepsis in mice with TLR4 that received LPS pretreatment or posttreatment. Survival was associated with reduced bacterial burden and serum cytokine concentrations. Death was associated with abnormal liver function and blood glucose concentrations. Endotoxin tolerance improved survival in A/J and CBA/CaHN-Btkxid//J mice but not Rag-1 KO mice. Conclusions TLR4 stimulation before or after S. pneumoniae infection improved survival and was dependent on T-cells but did not require an intact complement cascade or functional B cells. PMID:24465843

Influence of Depression and Hostility on Exercise Tolerance and Improvement in Patients with Coronary Heart Disease.

PubMed

Shen, Biing-Jiun; Gau, Jen-Tzer

2017-04-01

Although hostility and depression have been linked to higher cardiac risk and poor prognosis of patients with coronary heart disease (CHD), there is a lack of research that studies how they may influence the short-term outcomes among patients participating in cardiac rehabilitation (CR). This study aimed to investigate the influence of hostility and depression on patients' exercise tolerance and improvement trajectory in a CR program over 6 weeks. Participants were 142 patients with CHD, with a mean age of 62 years. Latent growth curve modeling was conducted to determine whether hostility and depression predicted patients' baseline exercise tolerance and rates of improvement on treadmill, while controlling for age and severity of illness. In addition, analysis was conducted to examine whether depression mediated the influence of hostility on exercise outcomes. Patients with CHD with higher hostility scores had a lower baseline exercise tolerance and slower rates of improvement over 6 weeks. Depressive symptom severity mediated the influence of hostility on exercise baseline and improvement. Patients with higher hostility were more likely to have more severe depressive symptoms, which in turn were associated with lower baseline exercise tolerance and slower improvement. While both hostility and depression predicted the exercise outcomes in CR, depression explained the influence of hostility. The findings underscore the importance of addressing psychosocial issues in treatment of CHD patients and provide support for psychosocial interventions in CR to facilitate patients' recovery.

Autophagy Differentially Regulates Insulin Production and Insulin Sensitivity.

PubMed

Yamamoto, Soh; Kuramoto, Kenta; Wang, Nan; Situ, Xiaolei; Priyadarshini, Medha; Zhang, Weiran; Cordoba-Chacon, Jose; Layden, Brian T; He, Congcong

2018-06-12

Autophagy, a stress-induced lysosomal degradative pathway, has been assumed to exert similar metabolic effects in different organs. Here, we establish a model where autophagy plays different roles in insulin-producing β cells versus insulin-responsive cells, utilizing knockin (Becn1 F121A ) mice manifesting constitutively active autophagy. With a high-fat-diet challenge, the autophagy-hyperactive mice unexpectedly show impaired glucose tolerance, but improved insulin sensitivity, compared to mice with normal autophagy. Autophagy hyperactivation enhances insulin signaling, via suppressing ER stress in insulin-responsive cells, but decreases insulin secretion by selectively sequestrating and degrading insulin granule vesicles in β cells, a process we term "vesicophagy." The reduction in insulin storage, insulin secretion, and glucose tolerance is reversed by transient treatment of autophagy inhibitors. Thus, β cells and insulin-responsive tissues require different autophagy levels for optimal function. To improve insulin sensitivity without hampering secretion, acute or intermittent, rather than chronic, activation of autophagy should be considered in diabetic therapy development. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Measuring the ambiguity tolerance of medical students: a cross-sectional study from the first to sixth academic years

PubMed Central

2014-01-01

Background Tolerance of ambiguity, or the extent to which ambiguous situations are perceived as desirable, is an important component of the attitudes and behaviors of medical students. However, few studies have compared this trait across the years of medical school. General practitioners are considered to have a higher ambiguity tolerance than specialists. We compared ambiguity tolerance between general practitioners and medical students. Methods We designed a cross-sectional study to evaluate the ambiguity tolerance of 622 medical students in the first to sixth academic years. We compared this with the ambiguity tolerance of 30 general practitioners. We used the inventory for measuring ambiguity tolerance (IMA) developed by Reis (1997), which includes three measures of ambiguity tolerance: openness to new experiences, social conflicts, and perception of insoluble problems. Results We obtained a total of 564 complete data sets (return rate 90.1%) from medical students and 29 questionnaires (return rate 96.7%) from general practitioners. In relation to the reference groups defined by Reis (1997), medical students had poor ambiguity tolerance on all three scales. No differences were found between those in the first and the sixth academic years, although we did observe gender-specific differences in ambiguity tolerance. We found no differences in ambiguity tolerance between general practitioners and medical students. Conclusions The ambiguity tolerance of the students that we assessed was below average, and appeared to be stable throughout the course of their studies. In contrast to our expectations, the general practitioners did not have a higher level of ambiguity tolerance than the students did. PMID:24405525

Measuring the ambiguity tolerance of medical students: a cross-sectional study from the first to sixth academic years.

PubMed

Weissenstein, Anne; Ligges, Sandra; Brouwer, Britta; Marschall, Bernhard; Friederichs, Hendrik

2014-01-09

Tolerance of ambiguity, or the extent to which ambiguous situations are perceived as desirable, is an important component of the attitudes and behaviors of medical students. However, few studies have compared this trait across the years of medical school. General practitioners are considered to have a higher ambiguity tolerance than specialists. We compared ambiguity tolerance between general practitioners and medical students. We designed a cross-sectional study to evaluate the ambiguity tolerance of 622 medical students in the first to sixth academic years. We compared this with the ambiguity tolerance of 30 general practitioners. We used the inventory for measuring ambiguity tolerance (IMA) developed by Reis (1997), which includes three measures of ambiguity tolerance: openness to new experiences, social conflicts, and perception of insoluble problems. We obtained a total of 564 complete data sets (return rate 90.1%) from medical students and 29 questionnaires (return rate 96.7%) from general practitioners. In relation to the reference groups defined by Reis (1997), medical students had poor ambiguity tolerance on all three scales. No differences were found between those in the first and the sixth academic years, although we did observe gender-specific differences in ambiguity tolerance. We found no differences in ambiguity tolerance between general practitioners and medical students. The ambiguity tolerance of the students that we assessed was below average, and appeared to be stable throughout the course of their studies. In contrast to our expectations, the general practitioners did not have a higher level of ambiguity tolerance than the students did.

Generation of American elm trees with tolerance to Dutch elm disease through controlled crosses and selection

Treesearch

James M. Slavicek; Kathleen S. Knight

2012-01-01

The goal of our research and development efforts is to generate new and/or improved selections of the American elm (Ulmus americana L.) with tolerance/resistance to Dutch elm disease (DED). The approaches we are taking for this effort include: 1) controlled breeding using known DED -tolerant selections, 2) controlled breeding using DED-tolerant...

Genomic Selection Improves Heat Tolerance in Dairy Cattle

PubMed Central

Garner, J. B.; Douglas, M. L.; Williams, S. R. O; Wales, W. J.; Marett, L. C.; Nguyen, T. T. T.; Reich, C. M.; Hayes, B. J.

2016-01-01

Dairy products are a key source of valuable proteins and fats for many millions of people worldwide. Dairy cattle are highly susceptible to heat-stress induced decline in milk production, and as the frequency and duration of heat-stress events increases, the long term security of nutrition from dairy products is threatened. Identification of dairy cattle more tolerant of heat stress conditions would be an important progression towards breeding better adapted dairy herds to future climates. Breeding for heat tolerance could be accelerated with genomic selection, using genome wide DNA markers that predict tolerance to heat stress. Here we demonstrate the value of genomic predictions for heat tolerance in cohorts of Holstein cows predicted to be heat tolerant and heat susceptible using controlled-climate chambers simulating a moderate heatwave event. Not only was the heat challenge stimulated decline in milk production less in cows genomically predicted to be heat-tolerant, physiological indicators such as rectal and intra-vaginal temperatures had reduced increases over the 4 day heat challenge. This demonstrates that genomic selection for heat tolerance in dairy cattle is a step towards securing a valuable source of nutrition and improving animal welfare facing a future with predicted increases in heat stress events. PMID:27682591

Comparison of Flow and Volume Incentive Spirometry on Pulmonary Function and Exercise Tolerance in Open Abdominal Surgery: A Randomized Clinical Trial.

PubMed

Kumar, Amaravadi Sampath; Alaparthi, Gopala Krishna; Augustine, Alfred Joseph; Pazhyaottayil, Zulfeequer Chundaanveetil; Ramakrishna, Anand; Krishnakumar, Shyam Krishnan

2016-01-01

Surgical procedures in abdominal area lead to changes in pulmonary function, respiratory mechanics and impaired physical capacity leading to postoperative pulmonary complications, which can affect up to 80% of upper abdominal surgery. To evaluate the effects of flow and volume incentive spirometry on pulmonary function and exercise tolerance in patients undergoing open abdominal surgery. A randomized clinical trial was conducted in a hospital of Mangalore city in Southern India. Thirty-seven males and thirteen females who were undergoing abdominal surgeries were included and allocated into flow and volume incentive spirometry groups by block randomization. All subjects underwent evaluations of pulmonary function with measurement of Forced Vital Capacity (FVC), Forced Expiratory Volume in the first second (FEV1), Peak Expiratory Flow (PEF). Preoperative and postoperative measurements were taken up to day 5 for both groups. Exercise tolerance measured by Six- Minute Walk Test during preoperative period and measured again at the time of discharge for both groups. Pulmonary function was analysed by post-hoc analysis and carried out using Bonferroni's 't'-test. Exercise tolerance was analysed by Paired 'T'-test. Pulmonary function (FVC, FEV1, and PEFR) was found to be significantly decreased in 1(st), 2(nd) and 3(rd) postoperative day when compared with preoperative day. On 4(th) and 5(th) postoperative day the pulmonary function (FVC, FEV1, and PEFR) was found to be better preserved in both flow and volume incentive spirometry groups. The Six-Minute Walk Test showed a statistically significant improvement in pulmonary function on the day of discharge than in the preoperative period. In terms of distance covered, the volume- incentive spirometry group showed a greater statistically significant improvement from the preoperative period to the time of discharge than was exhibited by the flow incentive spirometry group. Flow and volume incentive spirometry can be safely recommended to patients undergoing open abdominal surgery as there have been no adverse events recorded. Also, these led to a demonstrable improvement in pulmonary function and exercise tolerance.

Comparison of Flow and Volume Incentive Spirometry on Pulmonary Function and Exercise Tolerance in Open Abdominal Surgery: A Randomized Clinical Trial

PubMed Central

Kumar, Amaravadi Sampath; Augustine, Alfred Joseph; Pazhyaottayil, Zulfeequer Chundaanveetil; Ramakrishna, Anand; Krishnakumar, Shyam Krishnan

2016-01-01

Introduction Surgical procedures in abdominal area lead to changes in pulmonary function, respiratory mechanics and impaired physical capacity leading to postoperative pulmonary complications, which can affect up to 80% of upper abdominal surgery. Aim To evaluate the effects of flow and volume incentive spirometry on pulmonary function and exercise tolerance in patients undergoing open abdominal surgery. Materials and Methods A randomized clinical trial was conducted in a hospital of Mangalore city in Southern India. Thirty-seven males and thirteen females who were undergoing abdominal surgeries were included and allocated into flow and volume incentive spirometry groups by block randomization. All subjects underwent evaluations of pulmonary function with measurement of Forced Vital Capacity (FVC), Forced Expiratory Volume in the first second (FEV1), Peak Expiratory Flow (PEF). Preoperative and postoperative measurements were taken up to day 5 for both groups. Exercise tolerance measured by Six- Minute Walk Test during preoperative period and measured again at the time of discharge for both groups. Pulmonary function was analysed by post-hoc analysis and carried out using Bonferroni’s ‘t’-test. Exercise tolerance was analysed by Paired ‘T’-test. Results Pulmonary function (FVC, FEV1, and PEFR) was found to be significantly decreased in 1st, 2nd and 3rd postoperative day when compared with preoperative day. On 4th and 5th postoperative day the pulmonary function (FVC, FEV1, and PEFR) was found to be better preserved in both flow and volume incentive spirometry groups. The Six-Minute Walk Test showed a statistically significant improvement in pulmonary function on the day of discharge than in the preoperative period. In terms of distance covered, the volume- incentive spirometry group showed a greater statistically significant improvement from the preoperative period to the time of discharge than was exhibited by the flow incentive spirometry group. Conclusion Flow and volume incentive spirometry can be safely recommended to patients undergoing open abdominal surgery as there have been no adverse events recorded. Also, these led to a demonstrable improvement in pulmonary function and exercise tolerance. PMID:26894090

Comparative analysis of transcriptome in two wheat genotypes with contrasting levels of drought tolerance

USDA-ARS?s Scientific Manuscript database

Drought tolerance is a complex trait that is governed by multiple genes. To identify the potential candidate genes, comparative analysis of drought stress-responsive transcriptome between drought-tolerant (Triticum aestivum Cv. C306) and drought-sensitive (Triticum aestivum Cv. WL711) genotypes was ...

The negative effect of starvation and the positive effect of mild thermal stress on thermal tolerance of the red flour beetle, Tribolium castaneum

NASA Astrophysics Data System (ADS)

Scharf, Inon; Wexler, Yonatan; MacMillan, Heath Andrew; Presman, Shira; Simson, Eddie; Rosenstein, Shai

2016-04-01

The thermal tolerance of a terrestrial insect species can vary as a result of differences in population origin, developmental stage, age, and sex, as well as via phenotypic plasticity induced in response to changes in the abiotic environment. Here, we studied the effects of both starvation and mild cold and heat shocks on the thermal tolerance of the red flour beetle, Tribolium castaneum. Starvation led to impaired cold tolerance, measured as chill coma recovery time, and this effect, which was stronger in males than females, persisted for longer than 2 days but less than 7 days. Heat tolerance, measured as heat knockdown time, was not affected by starvation. Our results highlight the difficulty faced by insects when encountering multiple stressors simultaneously and indicate physiological trade-offs. Both mild cold and heat shocks led to improved heat tolerance in both sexes. It could be that both mild shocks lead to the expression of heat shock proteins, enhancing heat tolerance in the short run. Cold tolerance was not affected by previous mild cold shock, suggesting that such a cold shock, as a single event, causes little stress and hence elicits only weak physiological reaction. However, previous mild heat stress led to improved cold tolerance but only in males. Our results point to both hardening and cross-tolerance between cold and heat shocks.

Dronedarone: current evidence and future questions.

PubMed

Schafer, Jeremy A; Kjesbo, Nicole K; Gleason, Patrick P

2010-01-01

Atrial fibrillation (AF) is the most common sustained arrhythmia, affecting more than 2.2 million Americans. ACC/AHA/ESC guidelines for the management of patients with AF recommend amiodarone for maintaining sinus rhythm. Dronedarone is a derivative of amiodarone indicated for the treatment of AF. To provide an overview of dronedarone with a focus on the phase III trials and discuss unresolved questions of dronedarone. A literature search was conducted via the PubMed database using the keyword "dronedarone." Search was limited to human trials in english. The FDA website was searched for briefing documents and subcommittee meetings on dronedarone. Clinicaltrials.gov was searched with the keyword dronedarone for upcoming or unpublished clinical trials. Five phase III trials are available for dronedarone: ANDROMEDA, EURIDIS/ADONIS, ATHENA, ERATO, and DIONYSIS. EURIDIS/ADONIS and ATHENA demonstrated a reduction AF recurrence with dronedarone compared to placebo. The ANDROMEDA trial recruited patients with recent hospitalization for heart failure and was terminated due to an excess of deaths in the dronedarone group. The DIONYSIS trial was a comparative effectiveness trial that demonstrated less efficacy for dronedarone but improved tolerability compared to amiodarone. Dronedarone represents an option in the management of AF in select patients. Dronedarone is not appropriate in patients with recently decompensated heart failure or those treated with strong CYP3A4 inhibitors or medications prolonging the QT interval. Dronedarone appears to have improved tolerability at the expense of decreased efficacy when compared to amiodarone. Questions remain on the long-term safety, use in patients with heart failure, retreatment after dronedarone or amiodarone failure, and comparative efficacy with a rate control strategy.

Cyber situation awareness: modeling detection of cyber attacks with instance-based learning theory.

PubMed

Dutt, Varun; Ahn, Young-Suk; Gonzalez, Cleotilde

2013-06-01

To determine the effects of an adversary's behavior on the defender's accurate and timely detection of network threats. Cyber attacks cause major work disruption. It is important to understand how a defender's behavior (experience and tolerance to threats), as well as adversarial behavior (attack strategy), might impact the detection of threats. In this article, we use cognitive modeling to make predictions regarding these factors. Different model types representing a defender, based on Instance-Based Learning Theory (IBLT), faced different adversarial behaviors. A defender's model was defined by experience of threats: threat-prone (90% threats and 10% nonthreats) and nonthreat-prone (10% threats and 90% nonthreats); and different tolerance levels to threats: risk-averse (model declares a cyber attack after perceiving one threat out of eight total) and risk-seeking (model declares a cyber attack after perceiving seven threats out of eight total). Adversarial behavior is simulated by considering different attack strategies: patient (threats occur late) and impatient (threats occur early). For an impatient strategy, risk-averse models with threat-prone experiences show improved detection compared with risk-seeking models with nonthreat-prone experiences; however, the same is not true for a patient strategy. Based upon model predictions, a defender's prior threat experiences and his or her tolerance to threats are likely to predict detection accuracy; but considering the nature of adversarial behavior is also important. Decision-support tools that consider the role of a defender's experience and tolerance to threats along with the nature of adversarial behavior are likely to improve a defender's overall threat detection.

Comparison between pre-exercise casein peptide and intact casein supplementation on glucose tolerance in mice fed a high-fat diet.

PubMed

Matsunaga, Yutaka; Tamura, Yuki; Sakata, Yasuyuki; Nonaka, Yudai; Saito, Noriko; Nakamura, Hirohiko; Shimizu, Takashi; Takeda, Yasuhiro; Terada, Shin; Hatta, Hideo

2018-04-01

We hypothesized that along with exercise, casein peptide supplementation would have a higher impact on improving glucose tolerance than intact casein. Male 6-week-old ICR mice were provided a high-fat diet to induce obesity and glucose intolerance. The mice were randomly divided into 4 treatment groups: control (Con), endurance training (Tr), endurance training with intact casein supplementation (Cas+Tr), and endurance training with casein peptide supplementation (CP+Tr). The mice in each group were orally administrated water, intact casein, or casein peptide (1.0 mg/g body weight, every day), and then subjected to endurance training (15-25 m/min, 60 min, 5 times/week for 4 weeks) on a motor-driven treadmill 30 min after ingestion. Our results revealed that total intra-abdominal fat was significantly lower in CP+Tr than in Con (p < 0.05). Following an oral glucose tolerance test, the blood glucose area under the curve (AUC) was found to be significantly smaller for CP+Tr than for Con (p < 0.05). Moreover, in the soleus muscle, glucose transporter 4 (GLUT4) protein levels were significantly higher in CP+Tr than in Con (p < 0.01). However, intra-abdominal fat, blood glucose AUC, and GLUT4 protein content in the soleus muscle did not alter in Tr and Cas+Tr when compared with Con. These observations suggest that pre-exercise casein peptide supplementation has a higher effect on improving glucose tolerance than intact casein does in mice fed a high-fat diet.

Nitrogen-Deficiency Stress Induces Protein Expression Differentially in Low-N Tolerant and Low-N Sensitive Maize Genotypes

PubMed Central

Nazir, Muslima; Pandey, Renu; Siddiqi, Tariq O.; Ibrahim, Mohamed M.; Qureshi, Mohammad I.; Abraham, Gerard; Vengavasi, Krishnapriya; Ahmad, Altaf

2016-01-01

Nitrogen (N) is essential for proper plant growth and its application has proven to be critical for agricultural produce. However, for unavoidable economic and environmental problems associated with excessive use of N-fertilizers, it is an urgent demand to manage application of fertilizers. Improving the N-use efficiency (NUE) of crop plants to sustain productivity even at low N levels is the possible solution. In the present investigation, contrasting low-N sensitive (HM-4) and low-N tolerant (PEHM-2) genotypes were identified and used for comparative proteome-profiling of leaves under optimum and low N as well as restoration of low N on 3rd (NR3) and 5th (NR5) days after re-supplying N. The analysis of differential expression pattern of proteins was performed by 2-D gel electrophoresis. Significant variations in the expression of proteins were observed under low N, which were genotype specific. In the leaf proteome, 25 spots were influenced by N treatment and four spots were different between the two genotypes. Most of the proteins that were differentially accumulated in response to N level and were involved in photosynthesis and metabolism, affirming the relationship between N and carbon metabolism. In addition to this, greater intensity of some defense proteins in the low N tolerant genotype was found that may have a possible role in imparting it tolerance under N starvation conditions. The new insights generated on maize proteome in response to N-starvation and restoration would be useful toward improvement of NUE in maize. PMID:27047497

The combined effect of glass buffer strips and stitching on the damage tolerance of composites

NASA Technical Reports Server (NTRS)

Kullerd, Susan M.

1993-01-01

Recent research has demonstrated that through-the-thickness stitching provides major improvements in the damage tolerance of composite laminates loaded in compression. However, the brittle nature of polymer matrix composites makes them susceptible to damage propagation, requiring special material applications and designs to limit damage growth. Glass buffer strips, embedded within laminates, have shown the potential for improving the damage tolerance of unstitched composite laminates loaded in tension. The glass buffer strips, less stiff than the surrounding carbon fibers, arrest crack growth in composites under tensile loads. The present study investigates the damage tolerance characteristics of laminates that contain both stitching and glass buffer strips.

Overview of the U.S. DOE Accident Tolerant Fuel Development Program

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jon Carmack; Frank Goldner; Shannon M. Bragg-Sitton

2013-09-01

The United States Fuel Cycle Research and Development Advanced Fuels Campaign has been given the responsibility to conduct research and development on enhanced accident tolerant fuels with the goal of performing a lead test assembly or lead test rod irradiation in a commercial reactor by 2022. The Advanced Fuels Campaign has defined fuels with enhanced accident tolerance as those that, in comparison with the standard UO2-Zircaloy system currently used by the nuclear industry, can tolerate loss of active cooling in the reactor core for a considerably longer time period (depending on the LWR system and accident scenario) while maintaining ormore » improving the fuel performance during normal operations and operational transients, as well as design-basis and beyond design-basis events. This paper provides an overview of the FCRD Accident Tolerant Fuel program. The ATF attributes will be presented and discussed. Attributes identified as potentially important to enhance accident tolerance include reduced hydrogen generation (resulting from cladding oxidation), enhanced fission product retention under severe accident conditions, reduced cladding reaction with high-temperature steam, and improved fuel-cladding interaction for enhanced performance under extreme conditions. To demonstrate the enhanced accident tolerance of candidate fuel designs, metrics must be developed and evaluated using a combination of design features for a given LWR design, potential improvements to that design, and the design of an advanced fuel/cladding system. The aforementioned attributes provide qualitative guidance for parameters that will be considered for fuels with enhanced accident tolerance. It may be unnecessary to improve in all attributes and it is likely that some attributes or combination of attributes provide meaningful gains in accident tolerance, while others may provide only marginal benefits. Thus, an initial step in program implementation will be the development of quantitative metrics. A companion paper in these proceedings provides an update on the status of establishing these quantitative metrics for accident tolerant LWR fuel.1 The United States FCRD Advanced Fuels Campaign has embarked on an aggressive schedule for development of enhanced accident tolerant LWR fuels. The goal of developing such a fuel system that can be deployed in the U.S. LWR fleet in the next 10 to 20 years supports the sustainability of clean nuclear power generation in the United States.« less

Overexpression of AtPYL5 under the control of guard cell specific promoter improves drought stress tolerance in Arabidopsis.

PubMed

Quan, Wenli; Hu, Yuanlei; Mu, Zixin; Shi, Haitao; Chan, Zhulong

2018-05-31

PYR/PYLs function as ABA receptors and are key regulators during plant drought stress response. Previously we screened drought tolerance of Arabidopsis ABA receptors PYR/PYLs under the control of five different promoters. In this study, we characterized drought stress tolerance of AtPYL5 transgene under the control of one guard cell specific promoter, pGC1. pGC1::AtPYL5 transgenic Arabidopsis exhibited reduced transpiration rate and decreased water loss after drought treatment. Transformation of pGC1::AtPYL5 in Arabidopsis also decreased oxidative stress damage and improved photosynthesis under drought stress condition. These results indicated that pGC1::AtPYL5 construct is effective and might pave new way to develop genetically engineered plants to improve drought stress tolerance. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Glycine betaine improves oxidative stress tolerance and biocontrol efficacy of the antagonistic yeast Cystofilobasidium infirmominiatum

USDA-ARS?s Scientific Manuscript database

The effect of hydrogen peroxide-induced oxidative stress on the viability of the yeast antagonist, Cystofilobasidium infirmominiatum, as well as the effect of exogenous glycine betaine (GB) on yeast viability under oxidative stress, was determined. GB treatment improved the tolerance of C. infirmom...

Differential Modulation of Photosynthesis, Signaling, and Transcriptional Regulation between Tolerant and Sensitive Tomato Genotypes under Cold Stress

PubMed Central

Zhang, Junhong; Wang, Taotao; Li, Hanxia; Zhang, Yuyang; Yu, Chuying; Ye, Zhibiao

2012-01-01

The wild species Solanum habrochaites is more cold tolerant than the cultivated tomato (S. lycopersicum). To explore the mechanisms underlying cold tolerance of S. habrochaites, seedlings of S. habrochaites LA1777 introgression lines (ILs), as well as the two parents, were evaluated under low temperature (4°C). The IL LA3969 and its donor parent LA1777 were found to be more cold tolerant than the recurrent parent S. lycopersicum LA4024. The differences in physiology and global gene expression between cold-tolerant (LA1777 and LA3969) and -sensitive (LA4024) genotypes under cold stress were further investigated. Comparative transcriptome analysis identified 1613, 1456, and 1523 cold-responsive genes in LA1777, LA3969, and LA4024, respectively. Gene ontology (GO) term enrichment analysis revealed that more GO biological process terms were significantly enriched among the up-regulated genes in the two tolerant genotypes, whereas more biological processes were significantly repressed by cold stress in the sensitive one. A total of 92 genes with significant differential expression between tolerant and sensitive genotypes under cold stress were identified. Among these, many stress-related GO terms were significantly enriched, such as ‘response to stimulus’ and ‘response to stress’. Moreover, GO terms ‘response to hormone stimulus’, ‘response to reactive oxygen species (ROS)’, and ‘calcium-mediated signaling’ were also overrepresented. Several transcripts involved in hormone or ROS homeostasis were also differentially expressed. ROS, hormones, and calcium as signaling molecules may play important roles in regulating gene expression in response to cold stress. Moreover, the expression of various transcription factors, post-translational proteins, metabolic enzymes, and photosynthesis-related genes was also specifically modulated. These specific modifications may play pivotal roles in conferring cold tolerance in tomato. These results not only provide new insights into the molecular mechanisms of cold tolerance in tomato, but also provide potential candidate genes for genetic improvement. PMID:23226384

Proteomic Techniques and Management of Flooding Tolerance in Soybean.

PubMed

Komatsu, Setsuko; Tougou, Makoto; Nanjo, Yohei

2015-09-04

Climate change is considered a major threat to world agriculture and food security. To improve the agricultural productivity and sustainability, the development of high-yielding stress-tolerant, and climate-resilient crops is essential. Of the abiotic stresses, flooding stress is a very serious hazard because it markedly reduces plant growth and grain yield. Proteomic analyses indicate that the effects of flooding stress are not limited to oxygen deprivation but include many other factors. Although many flooding response mechanisms have been reported, flooding tolerance mechanisms have not been fully clarified for soybean. There were limitations in soybean materials, such as mutants and varieties, while they were abundant in rice and Arabidopsis. In this review, plant proteomic technologies are introduced and flooding tolerance mechanisms of soybeans are summarized to assist in the improvement of flooding tolerance in soybeans. This work will expedite transgenic or marker-assisted genetic enhancement studies in crops for developing high-yielding stress-tolerant lines or varieties under abiotic stress.

Regulation of extrarenal potassium homeostasis by adrenal hormones in rats.

PubMed

Bia, M J; Tyler, K A; DeFronzo, R A

1982-06-01

The effect of chronic (7-10 days) adrenal insufficiency on extrarenal potassium tolerance was examined by infusing potassium into rats after acute nephrectomy. The increment in plasma potassium concentration was significantly higher in glucocorticoid-replaced adrenalectomized rats versus controls (max delta PK 3.59 +/-0.11 vs. 2.93 +/- 0.08 meq/liter; P less than 0.001). The impairment in extrarenal potassium tolerance in adrenalectomized rats could not be attributed to acidemia, hypotension, changes in plasma insulin or glucose concentration, or potassium retention prior to study. Acute replacement with aldosterone resulted in significant improvement in the rise in plasma potassium after KCl (max delta PK 3.18 +/- 0.06 meq/liter; P less than 0.005 compared with aldosterone-deficient adrenalectomized rats but higher than in controls, P less than 0.02). If given on a chronic basis, aldosterone replacement led to a complete correction of the defect (max delta PK = 2.89 +/- 0.08 meq/liter). Acute epinephrine replacement in adrenalectomized rats also returned potassium tolerance to normal (max delta PK = 3.02 +/- 0.10 meq/liter). The results demonstrate that extrarenal potassium tolerance is impaired in chronic adrenal insufficiency and suggest that both aldosterone and epinephrine deficiency may contribute to the defect, since replacement with either hormone returns potassium tolerance toward normal. Accordingly, both aldosterone and epinephrine have important extrarenal mechanisms of action.

Actinobase: Database on molecular diversity, phylogeny and biocatalytic potential of salt tolerant alkaliphilic actinomycetes.

PubMed

Sharma, Amit K; Gohel, Sangeeta; Singh, Satya P

2012-01-01

Actinobase is a relational database of molecular diversity, phylogeny and biocatalytic potential of haloalkaliphilic actinomycetes. The main objective of this data base is to provide easy access to range of information, data storage, comparison and analysis apart from reduced data redundancy, data entry, storage, retrieval costs and improve data security. Information related to habitat, cell morphology, Gram reaction, biochemical characterization and molecular features would allow researchers in understanding identification and stress adaptation of the existing and new candidates belonging to salt tolerant alkaliphilic actinomycetes. The PHP front end helps to add nucleotides and protein sequence of reported entries which directly help researchers to obtain the required details. Analysis of the genus wise status of the salt tolerant alkaliphilic actinomycetes indicated 6 different genera among the 40 classified entries of the salt tolerant alkaliphilic actinomycetes. The results represented wide spread occurrence of salt tolerant alkaliphilic actinomycetes belonging to diverse taxonomic positions. Entries and information related to actinomycetes in the database are publicly accessible at http://www.actinobase.in. On clustalW/X multiple sequence alignment of the alkaline protease gene sequences, different clusters emerged among the groups. The narrow search and limit options of the constructed database provided comparable information. The user friendly access to PHP front end facilitates would facilitate addition of sequences of reported entries. The database is available for free at http://www.actinobase.in.

Ectopic Expression of a Glycine soja myo-Inositol Oxygenase Gene (GsMIOX1a) in Arabidopsis Enhances Tolerance to Alkaline Stress

PubMed Central

Chen, Chen; Sun, Xiaoli; Duanmu, Huizi; Yu, Yang; Liu, Ailin; Xiao, Jialei; Zhu, Yanming

2015-01-01

Myo-inositol participates in various aspects of plant physiology, and myo-inositol oxygenase is the key enzyme of the myo-inositol oxygenation pathway. Previous studies indicated that myo-inositol oxygenase may play a role in plant responses to abiotic stresses. In this study, we focused on the functional characterization of GsMIOX1a, a remarkable alkaline stress-responsive gene of Glycine soja 07256, based on RNA-seq data. Using quantitative real-time PCR, we demonstrated that GsMIOX1a is rapidly induced by alkaline stress and expressed predominantly in flowers. We also elucidated the positive function of GsMIOX1a in the alkaline response in the wild type, atmiox1 mutant as well as GsMIOX1a-overexpressing Arabidopsis. We determined that atmiox1 mutant decreased Arabidopsis tolerance to alkaline stress, whereas GsMIOX1a overexpression increased tolerance. Moreover, the expression levels of some alkaline stress-responsive and inducible marker genes, including H+-Ppase, NADP-ME, KIN1 and RD29B, were also up-regulated in GsMIOX1a overexpression lines compared with the wild type and atmiox1 mutant. Together, these results suggest that the GsMIOX1a gene positively regulates plant tolerance to alkaline stress. This is the first report to demonstrate that ectopic expression of myo-inositol oxygenase improves alkaline tolerance in plants. PMID:26091094

A 12-month, open-label, comparative study of quetiapine and risperidone in the acute and long-term treatment of schizophrenia.

PubMed

Perez, Victor; Cañas, Fernando; Tafalla, Monica

2008-05-01

This multicentre, observational, prospective, nonrandomized study compared the effectiveness and tolerability of quetiapine and risperidone in the acute and long-term treatment of schizophrenia in a clinical setting. Patients admitted to an acute unit with schizophrenia, schizophreniform or schizoaffective disorder (DSM-IV), who were prescribed quetiapine or risperidone (3 : 1 ratio) within the first week of treatment, according to the physician's usual practice, were recruited. In total, 492 patients (quetiapine: 367; risperidone: 125) were followed up at weeks 1 and 2, discharge and 6 and 12 months thereafter. Mean doses at 12 months were: quetiapine 718.5 mg/day and risperidone 7.0 mg/day. Efficacy measures (Brief Psychiatric Rating Scale, Clinical Global Impression Severity of Illness and Improvement) indicated similar results for both agents. No difference was found in rehospitalization rate with either drug. In terms of tolerability, orthostatic hypotension was more frequent with quetiapine, but extrapyramidal symptoms and male sexual dysfunction were more frequent with risperidone. In conclusion, quetiapine and risperidone had comparable effectiveness, but there were differences between treatments in their side effect profile.

Administration of pioglitazone alone or with alogliptin delays diabetes onset in UCD-T2DM rats

PubMed Central

Cummings, Bethany P; Bettaieb, Ahmed; Graham, James L; Stanhope, Kimber; Haj, Fawaz G; Havel, Peter J

2015-01-01

There is a need to identify strategies for type 2 diabetes prevention. Therefore, we investigated the efficacy of pioglitazone and alogliptin alone and in combination to prevent type 2 diabetes onset in UCD-T2DM rats, a model of polygenic obese type 2 diabetes. At 2 months of age, rats were divided into four groups: control, alogliptin (20 mg/kg per day), pioglitazone (2.5 mg/kg per day), and alogliptin+pioglitazone. Non-fasting blood glucose was measured weekly to determine diabetes onset. Pioglitazone alone and in combination with alogliptin lead to a 5-month delay in diabetes onset despite promoting increased food intake and body weight (BW). Alogliptin alone did not delay diabetes onset or affect food intake or BW relative to controls. Fasting plasma glucose, insulin, and lipid concentrations were lower and adiponectin concentrations were threefold higher in groups treated with pioglitazone. All treatment groups demonstrated improvements in glucose tolerance and insulin secretion during an oral glucose tolerance test with an additive improvement observed with alogliptin+pioglitazone. Islet histology revealed an improvement of islet morphology in all treatment groups compared with control. Pioglitazone treatment also resulted in increased expression of markers of mitochondrial biogenesis in brown adipose tissue and white adipose tissue, with mild elevations observed in animals treated with alogliptin alone. Pioglitazone markedly delays the onset of type 2 diabetes in UCD-T2DM rats through improvements of glucose tolerance, insulin sensitivity, islet function, and markers of adipose mitochondrial biogenesis; however, addition of alogliptin at a dose of 20 mg/kg per day to pioglitazone treatment does not enhance the prevention/delay of diabetes onset. PMID:24627447

Ectopic expression of wheat expansin gene TaEXPA2 improved the salt tolerance of transgenic tobacco by regulating Na+ /K+ and antioxidant competence.

PubMed

Chen, Yanhui; Han, Yangyang; Kong, Xiangzhu; Kang, Hanhan; Ren, Yuanqing; Wang, Wei

2017-02-01

High salinity is one of the most serious environmental stresses that limit crop growth. Expansins are cell wall proteins that regulate plant development and abiotic stress tolerance by mediating cell wall expansion. We studied the function of a wheat expansin gene, TaEXPA2, in salt stress tolerance by overexpressing it in tobacco. Overexpression of TaEXPA2 enhanced the salt stress tolerance of transgenic tobacco plants as indicated by the presence of higher germination rates, longer root length, more lateral roots, higher survival rates and more green leaves under salt stress than in the wild type (WT). Further, when leaf disks of WT plants were incubated in cell wall protein extracts from the transgenic tobacco plants, their chlorophyll content was higher under salt stress, and this improvement from TaEXPA2 overexpression in transgenic tobacco was inhibited by TaEXPA2 protein antibody. The water status of transgenic tobacco plants was improved, perhaps by the accumulation of osmolytes such as proline and soluble sugar. TaEXPA2-overexpressing tobacco lines exhibited lower Na + but higher K + accumulation than WT plants. Antioxidant competence increased in the transgenic plants because of the increased activity of antioxidant enzymes. TaEXPA2 protein abundance in wheat was induced by NaCl, and ABA signaling was involved. Gene expression regulation was involved in the enhanced salt stress tolerance of the TaEXPA2 transgenic plants. Our results suggest that TaEXPA2 overexpression confers salt stress tolerance on the transgenic plants, and this is associated with improved water status, Na + /K + homeostasis, and antioxidant competence. ABA signaling participates in TaEXPA2-regulated salt stress tolerance. © 2016 Scandinavian Plant Physiology Society.

Isolation and characterization of low-sulphur-tolerant mutants of Arabidopsis

PubMed Central

Wu, Yu; Zhao, Qing; Gao, Lei; Yu, Xiao-Min; Fang, Ping; Oliver, David J.; Xiang, Cheng-Bin

2010-01-01

Sulphur is an essential element for plant growth and development as well as for defence against biotic and abiotic stresses. Increasing sulphate utilization efficiency (SUE) is an important issue for crop improvement. Little is known about the genetic determinants of sulphate utilization efficiency. No gain-of-function mutants with improved SUE have been reported to date. Here the isolation and characterization of two low-sulphur-tolerant mutants, sue3 and sue4 are reported using a high-throughput genetic screen where a ‘sulphur-free’ solid medium was devised to give the selection pressure necessary to suppress the growth of the wild-type seedlings. Both mutants showed improved tolerance to low sulphur conditions and well-developed root systems. The mutant phenotype of both sue3 and sue4 was specific to sulphate deficiency and the mutants displayed enhanced tolerance to heavy metal and oxidative stress. Genetic analysis revealed that sue3 was caused by a single recessive nuclear mutation while sue4 was caused by a single dominant nuclear mutation. The recessive locus in sue3 is the previously identified VirE2-interacting Protein 1. The dominant locus in sue4 is a function-unknown locus activated by the four enhancers on the T-DNA. The function of SUE3 and SUE4 in low sulphur tolerance was confirmed either by multiple mutant alleles or by recapitulation analysis. Taken together, our results demonstrate that this genetic screen is a reasonable approach to isolate Arabidopsis mutants with improved low sulphur tolerance and potentially with enhanced sulphate utilization efficiency. The two loci identified in sue3 and sue4 should assist in understanding the molecular mechanisms of low sulphur tolerance. PMID:20547563

Isolation and characterization of low-sulphur-tolerant mutants of Arabidopsis.

PubMed

Wu, Yu; Zhao, Qing; Gao, Lei; Yu, Xiao-Min; Fang, Ping; Oliver, David J; Xiang, Cheng-Bin

2010-07-01

Sulphur is an essential element for plant growth and development as well as for defence against biotic and abiotic stresses. Increasing sulphate utilization efficiency (SUE) is an important issue for crop improvement. Little is known about the genetic determinants of sulphate utilization efficiency. No gain-of-function mutants with improved SUE have been reported to date. Here the isolation and characterization of two low-sulphur-tolerant mutants, sue3 and sue4 are reported using a high-throughput genetic screen where a 'sulphur-free' solid medium was devised to give the selection pressure necessary to suppress the growth of the wild-type seedlings. Both mutants showed improved tolerance to low sulphur conditions and well-developed root systems. The mutant phenotype of both sue3 and sue4 was specific to sulphate deficiency and the mutants displayed enhanced tolerance to heavy metal and oxidative stress. Genetic analysis revealed that sue3 was caused by a single recessive nuclear mutation while sue4 was caused by a single dominant nuclear mutation. The recessive locus in sue3 is the previously identified VirE2-interacting Protein 1. The dominant locus in sue4 is a function-unknown locus activated by the four enhancers on the T-DNA. The function of SUE3 and SUE4 in low sulphur tolerance was confirmed either by multiple mutant alleles or by recapitulation analysis. Taken together, our results demonstrate that this genetic screen is a reasonable approach to isolate Arabidopsis mutants with improved low sulphur tolerance and potentially with enhanced sulphate utilization efficiency. The two loci identified in sue3 and sue4 should assist in understanding the molecular mechanisms of low sulphur tolerance.

Supported treadmill ambulation for amyotrophic lateral sclerosis: a pilot study.

PubMed

Sanjak, Mohammed; Bravver, Elena; Bockenek, William L; Norton, H James; Brooks, Benjamin R

2010-12-01

To determine the feasibility, tolerability, safety, and exercise treatment-effect size of repetitive rhythmic exercise mediated by supported treadmill ambulation training (STAT) for patients with amyotrophic lateral sclerosis (ALS). Interventional with repeated-measures design. Multidisciplinary ALS clinic at academic medical center. Convenience sample of patients with ALS (N=9) who were ambulatory with assistive devices (Sinaki-Mulder stages II-III). Repetitive rhythmic exercise-STAT (30min total; 5min of exercise intercalated with 5min of rest) performed 3 times a week for 8 weeks. ALS Functional Rating Scale-Revised (ALSFRS-R), percentage of predicted vital capacity (VC), total lower-extremities manual muscle test (MMT), rate of perceived exertion (RPE), Fatigue Severity Scale (FSS), and maximum voluntary isometric contraction (MVIC) in 10 lower and 10 upper extremities. Gait performance, which included walking distance, speed, steps, and stride length, was evaluated during treadmill and ground 6-minute walk tests (6MWTs) and 25-foot walk test (25FWT). Feasibility issues decreased screened participants by 4 patients (31%). Nine patients were enrolled, but 6 patients (67%) completed the study and 3 (23% of original cohort; 33% of enrolled cohort) could not complete the exercise intervention because of non-ALS-related medical problems. Tolerability of the intervention measures during the treadmill 6MWT showed improvement in RPE (P≤.05) and FSS score (P≥.05). Safety measures (ALSFRS-R, VC, MMT) showed no decrease and showed statistical improvement in ALSFRS-R score (P≤.05) during the study interval. Exercise treatment-effect size showed variable improvements. Gait speed, distance, and stride length during the treadmill 6MWT improved significantly (P≤.05) after 4 weeks and improvements were maintained after 8 weeks compared with baseline. Walking distance during the ground 6MWT increased significantly after 4 weeks and was maintained after 8 weeks compared with baseline (P≤.05). Walking speed during the 25FWT and lower-extremity MVIC improved, but were not statistically significant. Repetitive rhythmic exercise-STAT is feasible, tolerated, and safe for patients with ALS. Repetitive rhythmic exercise-STAT treatment-effect size across a number of ALS-related measures was consistent with improved work capacity and gait function in patients with ALS who are dependent on assistive devices for ambulation. Repetitive rhythmic exercise-STAT should be evaluated further in larger studies to determine the stability of this improved function in relation to the rate of progression of the underlying ALS. Copyright © 2010 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Comparative Analysis of Disruption Tolerant Network Routing Simulations in the One and NS-3

DTIC Science & Technology

2017-12-01

real systems with less work compared to ns-2. In order to meet the design goals of ns-3, the entire code structure changed to a modular design . As a...NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA THESIS COMPARATIVE ANALYSIS OF DISRUPTION TOLERANT NETWORK ROUTING SIMULATIONS IN THE ONE AND NS-3...Thesis 03-23-2016 to 12-15-2017 4. TITLE AND SUBTITLE COMPARATIVE ANALYSIS OF DISRUPTION TOLERANT NETWORK ROUTING SIMULATIONS IN THE ONE AND NS-3 5

Overexpression of AtABCG25 enhances the abscisic acid signal in guard cells and improves plant water use efficiency.

PubMed

Kuromori, Takashi; Fujita, Miki; Urano, Kaoru; Tanabata, Takanari; Sugimoto, Eriko; Shinozaki, Kazuo

2016-10-01

In addition to improving drought tolerance, improvement of water use efficiency is a major challenge in plant physiology. Due to their trade-off relationships, it is generally considered that achieving stress tolerance is incompatible with maintaining stable growth. Abscisic acid (ABA) is a key phytohormone that regulates the balance between intrinsic growth and environmental responses. Previously, we identified AtABCG25 as a cell-membrane ABA transporter that export ABA from the inside to the outside of cells. AtABCG25-overexpressing plants showed a lower transpiration phenotype without any growth retardation. Here, we dissected this useful trait using precise phenotyping approaches. AtABCG25 overexpression stimulated a local ABA response in guard cells. Furthermore, AtABCG25 overexpression enhanced drought tolerance, probably resulting from maintenance of water contents over the common threshold for survival after drought stress treatment. Finally, we observed enhanced water use efficiency by overexpression of AtABCG25, in addition to drought tolerance. These results were consistent with the function of AtABCG25 as an ABA efflux transporter. This unique trait may be generally useful for improving the water use efficiency and drought tolerance of plants. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Glass ceramic ZERODUR enabling nanometer precision

NASA Astrophysics Data System (ADS)

Jedamzik, Ralf; Kunisch, Clemens; Nieder, Johannes; Westerhoff, Thomas

2014-03-01

The IC Lithography roadmap foresees manufacturing of devices with critical dimension of < 20 nm. Overlay specification of single digit nanometer asking for nanometer positioning accuracy requiring sub nanometer position measurement accuracy. The glass ceramic ZERODUR® is a well-established material in critical components of microlithography wafer stepper and offered with an extremely low coefficient of thermal expansion (CTE), the tightest tolerance available on market. SCHOTT is continuously improving manufacturing processes and it's method to measure and characterize the CTE behavior of ZERODUR® to full fill the ever tighter CTE specification for wafer stepper components. In this paper we present the ZERODUR® Lithography Roadmap on the CTE metrology and tolerance. Additionally, simulation calculations based on a physical model are presented predicting the long term CTE behavior of ZERODUR® components to optimize dimensional stability of precision positioning devices. CTE data of several low thermal expansion materials are compared regarding their temperature dependence between - 50°C and + 100°C. ZERODUR® TAILORED 22°C is full filling the tight CTE tolerance of +/- 10 ppb / K within the broadest temperature interval compared to all other materials of this investigation. The data presented in this paper explicitly demonstrates the capability of ZERODUR® to enable the nanometer precision required for future generation of lithography equipment and processes.

Results of a Multicenter, Randomized, Controlled Trial of a Hydrogen Peroxide-based Kit versus a Benzoyl Peroxide-based Kit in Mild-to-moderate Acne

PubMed Central

Micali, Giuseppe; Berardesca, Enzo; Dall’Oglio, Federica; Sinagra, Jo Linda; Guanziroli, Elena

2016-01-01

Objective:To evaluate the efficacy and tolerability of a novel hydrogen peroxide-based regimen versus a benzoyl peroxide-based regimen in mild-to-moderate acne. Methods: In this eight-week multicenter study, patients were randomized to either a hydrogen peroxide-based or a benzoyl peroxide-based regimen.The primary outcome measure of clinical response was assessed using the Global Acne Grading System (GAGS) at baseline,four weeks, and eight weeks. At Week 8, a patient self-satisfaction questionnaire was administered. Investigators were also queried at that time regarding assessment of tolerability and cosmetic acceptability. Tolerability was also measured at each visit. Results: Both treatment regimens were associated with improvement of GAGS score at Week 8 compared to baseline (p<0.0001). GAGS score did not differ significantly between the two regimens over the same period (p=0.7765). No significant adverse events were reported or observed in either treatment arm. Both patients and investigators found both regimens to be similarly effective and cosmetically acceptable. Conclusion: A novel hydrogen peroxide-based regimen was shown to be comparable in efficacy, safety, and cosmetic acceptability to a benzoyl peroxide-based regimen in the treatment of mild-to-moderate acne. PMID:27847549

Paclitaxel loaded phospholipid-based gel as a drug delivery system for local treatment of glioma.

PubMed

Chen, Tijia; Gong, Ting; Zhao, Ting; Liu, Xing; Fu, Yao; Zhang, Zhirong; Gong, Tao

2017-08-07

Paclitaxel (PTX) is a chemotherapeutic agent and has been widely used in clinic against human cancer. However, it has limited application in brain tumor treatment due to the poor penetration of blood brain barrier. Local delivery system is a promising carrier of PTX in the treatment of glioma. A biodegradable phospholipid-based gel (PG) system was developed for intratumoral injection and evaluated in brain glioma-bearing mice model. PTX loaded PG was composed of phospholipid, ethanol, medium chain triglyceride, triacetin and PTX. It was prepared by a very simple method. The system was a transparent solution with good fluidity, while turned into a gel after phase-transition when ethanol diffused. Both in vitro dissolution and in vivo imaging study proved the sustained release effect of PG system. In vivo tolerability study showed a better tolerability after mice treated with PTX PG compared with free PTX. The survival time of brain glioma-bearing mice after treatment with PTX PG was significantly prolonged compared with mice treated by free PTX (P<0.05). In conclusion, this study developed a novel PG based local PTX delivery system with simple preparation method, good tolerability and high therapeutic efficacy. It has a great potential to improve the clinical management of glioma. Copyright © 2017 Elsevier B.V. All rights reserved.

Adenoviral beta-adrenergic receptor kinase inhibitor gene transfer improves exercise capacity, cardiac contractility, and systemic inflammation in a model of pressure overload hypertrophy.

PubMed

Gupta, Dipin; Molina, Ezequiel J; Palma, Jon; Gaughan, John P; Long, Walter; Macha, Mahender

2008-10-01

We hypothesized that intracoronary adenoviral-mediated delivery of betaARKct would improve heart failure associated pathophysiologic abnormalities related to exercise capacity, cardiac contractility, systemic inflammation and volume overload. After aortic banding, a cohort of Sprague-Dawley rats was followed by echocardiography. When an absolute decline of 25% in fractional shortening was detected, animals were randomized to intracoronary delivery of Ad.ssARKct (n=14), Ad.beta-Gal (n=13), or followed without any other further intervention (n=18). Assessment of exercise tolerance and hemodynamic profile and measurement of markers of systemic inflammation and volume overload was performed at 7, 14, and 21 days after gene delivery. Data were analyzed using ANOVA. Animals receiving Ad.ssARKct showed improved exercise tolerance compared to Ad.Gal-treated animals at 14 days (507+/-26 s vs. 408+/-19 s, P=0.01) and 21 days (526+/-55 s vs. 323+/-19 s, P<0.001) following injection. Animals receiving Ad.ssARKct demonstrated improved +dP/dtmax (mean+/-SD, 5,581+/-960 mmHg/s vs. 3,134+/-438 mmHg/s, P<0.01) and -dP/dtmax (mean+/-SD, -3,494+/-1,269 mmHg/s vs. -1,925+/-638 mmHg/s, P<0.01) compared to Ad.Gal-treated animals at 7 days. These differences were observed up to 21 days following injection. Serum levels of IL-1, IL-6, and TNF-alpha, as well as ANP were also decreased in animals receiving Ad.betaARKct. Genetic modulation of heart failure using the betaARKct gene was associated with improved exercise capacity and cardiac function as well as amelioration in heart failure-associated profiles of systemic inflammation and volume overload.

Baseline severity but not gender modulates quantified Crataegus extract effects in early heart failure--a pooled analysis of clinical trials.

PubMed

Eggeling, Thomas; Regitz-Zagrosek, Vera; Zimmermann, Andrea; Burkart, Martin

2011-11-15

The efficacy of quantified Crataegus extract in chronic heart failure (CHF) has been assessed in numerous clinical studies. The present pooled analysis evaluates the impact of baseline severity and gender on objective and patient-reported endpoints and associations between both types of outcomes in patients with early CHF. Available data from 687 individual patients treated with quantified Crataegus extract or placebo in ten studies were pooled. Treatment effects on physiologic outcome parameters and on symptoms were analysed for their association with baseline severity and gender. Changes in symptom scores were investigated with respect to their relation to physiologic outcome parameters. Results were compared with observations in a 3-year cohort study. Physiologic outcome parameters maximal workload (MWL), left ventricular ejection fraction (LVEF) and pressure-heart rate product increase (PHRPI) at 50 W ergometric exercise improved more in active treatment than in placebo patients. Magnitude of improvement was independent from baseline for LVEF but increased for MWL and PHRPI with baseline severity. Improvement of typical symptoms like reduced exercise tolerance, exertional dyspnea, weakness, fatigue, and palpitations improved more with active treatment and in patients with more severe symptoms. A weak association between improvements in MWL, PRHP, and symptoms could be demonstrated. Gender differences in treatment effects could be explained by baseline differences. Results of the pooled analysis are in agreement with observations in the cohort study. Crataegus extract treatment effects on physiologic outcomes and typical symptoms were modulated by baseline severity. Taking baseline differences into account, benefits were comparable in male and female patients with impaired exercise-tolerance in early chronic heart-failure. Copyright © 2011 Elsevier GmbH. All rights reserved.

Cassia Cinnamon Supplementation Reduces Peak Blood Glucose Responses but Does Not Improve Insulin Resistance and Sensitivity in Young, Sedentary, Obese Women.

PubMed

Gutierrez, Jean L; Bowden, Rodney G; Willoughby, Darryn S

2016-01-01

Cassia cinnamon has been suggested to lower blood glucose (BG) and serum insulin (SI) due to an improvement in insulin resistance (IR) and sensitivity (IS). This study compared the effects Cassia cinnamon had on calculated IR and IS values and BG and SI in response to an oral glucose tolerance test (OGTT) in young, sedentary, and obese women. On three separate days, 10 women had a fasted venous blood sample obtained. Participants were given 5 g of encapsulated placebo (PLC) or 5 g of encapsulated Cassia cinnamon bark (CASS). Three hours after the initial blood sample, another blood sample was obtained to calculate values for IS and IR. The participants then completed an OGTT by consuming a 75 g glucose solution. Blood was obtained 30, 60, 90, and 120 min following glucose ingestion. IS and IR were not significantly different between placebo and Cassia (p > .05). The peak BG concentration in response to the OGTT was significantly lower at the 30 min time point for CASS, as compared to PLC (140 ± 5.8 and 156 ± 5.2 mg/dL, p = .025); however, there was no significant difference between treatments for SI (p > .05). The area-under-the-curve responses for BG and SI were not significantly different between PLC and CASS (p > .05). This study suggests that a 5 g dose of Cassia cinnamon may reduce the peak BG response and improve glucose tolerance following an OGTT, but with no improvement in IS and IR in young, sedentary, obese women.

FFA2 Contribution to Gestational Glucose Tolerance Is Not Disrupted by Antibiotics.

PubMed

Fuller, Miles; Li, Xiaoran; Fisch, Robert; Bughara, Moneb; Wicksteed, Barton; Kovatcheva-Datchary, Petia; Layden, Brian T

2016-01-01

During the insulin resistant phase of pregnancy, the mRNA expression of free fatty acid 2 receptor (Ffar2) is upregulated and as we recently reported, this receptor contributes to insulin secretion and pancreatic beta cell mass expansion in order to maintain normal glucose homeostasis during pregnancy. As impaired gestational glucose levels can affect metabolic health of offspring, we aimed to explore the role of maternal Ffar2 expression during pregnancy on the metabolic health of offspring and also the effects of antibiotics, which have been shown to disrupt gut microbiota fermentative activity (the source of the FFA2 ligands) on gestational glucose homeostasis. We found that maternal Ffar2 expression and impaired glucose tolerance during pregnancy had no effect on the growth rates, ad lib glucose and glucose tolerance in the offspring between 3 and 6 weeks of age. To disrupt short chain fatty acid production, we chronically treated WT mice and Ffar2-/- mice with broad range antibiotics and further compared their glucose tolerance prior to pregnancy and at gestational day 15, and also quantified cecum and plasma SCFAs. We found that during pregnancy antibiotic treatment reduced the levels of SCFAs in the cecum of the mice, but resulted in elevated levels of plasma SCFAs and altered concentrations of individual SCFAs. Along with these changes, gestational glucose tolerance in WT mice, but not Ffar2-/- mice improved while on antibiotics. Additional data showed that gestational glucose tolerance worsened in Ffar2-/- mice during a second pregnancy. Together, these results indicate that antibiotic treatment alone is inadequate to deplete plasma SCFA concentrations, and that modulation of gut microbiota by antibiotics does not disrupt the contribution of FFA2 to gestational glucose tolerance.

Opioid tolerance and urine drug testing among initiates of extended-release or long-acting opioids in Food and Drug Administration's Sentinel System.

PubMed

Larochelle, Marc R; Cocoros, Noelle M; Popovic, Jennifer; Dee, Elizabeth C; Kornegay, Cynthia; Ju, Jing; Racoosin, Judith A

A risk evaluation and mitigation strategy for extended-release and long-acting (ER/LA) opioid analgesics was approved by the Food and Drug Administration in 2012. Our objective was to assess frequency of opioid tolerance and urine drug testing for individuals initiating ER/LA opioid analgesics. Retrospective cohort study. Sentinel, a distributed database with electronic healthcare data on >190 million predominantly commercially insured members. Members under age 65 initiating ER/LA opioid analgesics between January 2009 and December 2013. We examined the proportion of opioid-tolerant-only ER/LA opioid analgesic initiates meeting tolerance criteria: receipt of ≥30 mg oxycodone equivalents per day in 7 days prior to the first opioid-tolerant-only dispensing. We separately examined the proportion of new users of extended-release oxycodone (ERO) and other ER/LA opioid analgesics with a claim for a urine drug test in the 30 days prior to, and separately for the 183 days after, dispensing. We identified 79,824 ERO, 7,343 extended-release hydromorphone, and 91,778 transdermal fentanyl opi-oid-tolerant-only episodes. Tolerance criteria were met in 64 percent of ERO, 64 percent of extended-release hydromorphone and 40 percent of transdermal fentanyl episodes. We identified 210,581 incident ERO and 311,660 other ER/LA opioid analgesic episodes. Use of urine drug testing for ERO compared with other ER/LA opioid analgesics was: 4 percent vs 14 percent respectively in the 30 days prior to initiation and 9 percent vs 23 percent respectively in the 183 days following initiation. These results suggest potential areas for improving appropriate ER/LA opioid analgesic prescribing practices.

Pre-gravid physical activity and reduced risk of glucose intolerance in pregnancy: the role of insulin sensitivity.

PubMed

Retnakaran, Ravi; Qi, Ying; Sermer, Mathew; Connelly, Philip W; Zinman, Bernard; Hanley, Anthony J G

2009-04-01

Pre-gravid physical activity has been associated with a reduced risk of gestational diabetes mellitus (GDM), although neither the types of exercise nor the physiologic mechanisms underlying this protective effect have been well-studied. Thus, we sought to study the relationships between types of pre-gravid physical activity and metabolic parameters in pregnancy, including glucose tolerance, insulin sensitivity and beta-cell function. A total of 851 women underwent a glucose challenge test (GCT) and a 3-h oral glucose tolerance test (OGTT) in late pregnancy, yielding four glucose tolerance groups: (i) GDM; (ii) gestational impaired glucose tolerance (GIGT); (iii) abnormal GCT with normal glucose tolerance on OGTT (abnormal GCT NGT); and (iv) normal GCT with NGT on OGTT (normal GCT NGT). Pre-gravid physical activity was assessed using the Baecke questionnaire, which measures (i) total physical activity and (ii) its three component domains: work, nonsport leisure-time, and vigorous/sports activity. Glucose tolerance status improved across increasing quartiles of pre-gravid total physical activity (P = 0.0244). Whereas neither work nor nonsport leisure-time activity differed between glucose tolerance groups, pre-gravid vigorous/sports activity was significantly higher in women with normal GCT NGT compared to women with (i) abnormal GCT NGT (P = 0.0018) (ii) GIGT (P = 0.0025), and (iii) GDM (P = 0.0044). In particular, vigorous/sports activity correlated with insulin sensitivity (measured by IS(OGTT)) (r = 0.21, P < 0.0001). Furthermore, on multiple linear regression analysis, pre-gravid vigorous/sports activity emerged as a significant independent predictor of IS(OGTT) in pregnancy (t = 4.97, P < 0.0001). Pre-gravid vigorous/sports activity is associated with a reduced risk of glucose intolerance in pregnancy, an effect likely mediated by enhanced insulin sensitivity.

Sub-zero cold tolerance of Spartina pectinata (prairie cordgrass) and Miscanthus × giganteus: candidate bioenergy crops for cool temperate climates

PubMed Central

Peixoto, Murilo de Melo; Lee, D. K.; Sage, Rowan F.

2015-01-01

Miscanthus × giganteus grown in cool temperate regions of North America and Europe can exhibit severe mortality in the year after planting, and poor frost tolerance of leaves. Spartina pectinata (prairie cordgrass), a productive C4 perennial grass native to North America, has been suggested as an alternative biofuel feedstock for colder regions; however, its cold tolerance relative to M. × giganteus is uncertain. Here, we compare the cold tolerance thresholds for winter-dormant rhizomes and spring/summer leaves of M. × giganteus and three accessions of S. pectinata. All genotypes were planted at a field site in Ontario, Canada. In November and February, the temperatures corresponding to 50% rhizome mortality (LT50) were near −24°C for S. pectinata and −4°C for M. × giganteus. In late April, the LT50 of rhizomes rose to −10°C for S. pectinata but remained near −4°C for M. × giganteus. Twenty percent of the M. × giganteus rhizomes collected in late April were dead while S. pectinata rhizomes showed no signs of winter injury. Photosynthesis and electrolyte leakage measurements in spring and summer demonstrate that S. pectinata leaves have greater frost tolerance in the field. For example, S. pectinata leaves remained viable above −9°C while the mortality threshold was near −5°C for M. × giganteus. These results indicate M. × giganteus will be unsuitable for production in continental interiors of cool-temperate climate zones unless freezing and frost tolerance are improved. By contrast, S. pectinata has the freezing and frost tolerance required for a higher-latitude bioenergy crop. PMID:25873680

High permeance sulfur tolerant Pd/Cu alloy membranes

DOEpatents

Ma, Yi Hua; Pomerantz, Natalie

2014-02-18

A method of making a membrane permeable to hydrogen gas (H.sub.2.uparw.) is disclosed. The membrane is made by forming a palladium layer, depositing a layer of copper on the palladium layer, and galvanically displacing a portion of the copper with palladium. The membrane has improved resistance to poisoning by H.sub.2S compared to a palladium membrane. The membrane also has increased permeance of hydrogen gas compared to palladium-copper alloys. The membrane can be annealed at a lower temperature for a shorter amount of time.

Genome-scale analyses of butanol tolerance in Saccharomyces cerevisiae reveal an essential role of protein degradation

PubMed Central

2013-01-01

Background n-Butanol and isobutanol produced from biomass-derived sugars are promising renewable transport fuels and solvents. Saccharomyces cerevisiae has been engineered for butanol production, but its high butanol sensitivity poses an upper limit to product titers that can be reached by further pathway engineering. A better understanding of the molecular basis of butanol stress and tolerance of S. cerevisiae is important for achieving improved tolerance. Results By combining a screening of the haploid S. cerevisiae knock-out library, gene overexpression, and genome analysis of evolutionary engineered n-butanol-tolerant strains, we established that protein degradation plays an essential role in tolerance. Strains deleted in genes involved in the ubiquitin-proteasome system and in vacuolar degradation of damaged proteins showed hypersensitivity to n-butanol. Overexpression of YLR224W, encoding the subunit responsible for the recognition of damaged proteins of an ubiquitin ligase complex, resulted in a strain with a higher n-butanol tolerance. Two independently evolved n-butanol-tolerant strains carried different mutations in both RPN4 and RTG1, which encode transcription factors involved in the expression of proteasome and peroxisomal genes, respectively. Introduction of these mutated alleles in the reference strain increased butanol tolerance, confirming their relevance in the higher tolerance phenotype. The evolved strains, in addition to n-butanol, were also more tolerant to 2-butanol, isobutanol and 1-propanol, indicating a common molecular basis for sensitivity and tolerance to C3 and C4 alcohols. Conclusions This study shows that maintenance of protein integrity plays an essential role in butanol tolerance and demonstrates new promising targets to engineer S. cerevisiae for improved tolerance. PMID:23552365

Moxonidine improves glycaemic control in mildly hypertensive, overweight patients: a comparison with metformin.

PubMed

Chazova, Irina; Almazov, Vladimir A; Shlyakhto, Evgeny

2006-07-01

To compare the effects of moxonidine and metformin on glycaemic control in patients with impaired glucose tolerance and signs of the metabolic syndrome. A multicentre, prospective, randomized, open-label study design was adopted with blinded endpoint evaluation. Patients > or =40 years old, with impaired glucose tolerance (or diabetes mellitus treated with diet alone) and a body mass index (BMI) of at least 27 kg/m2 were treated twice daily with moxonidine 0.2 mg or metformin 500 mg for 16 weeks. Oral glucose tolerance test (OGTT) was performed at baseline and end-of-study; plasma insulin and plasma glucose levels were measured at 0, 60, 120 and 180 min after administration. With regard to effects on insulin [mean area under the curve (AUC) for insulin], the primary efficacy endpoint of the study, both drugs did not show equivalence. On the contrary, in the per protocol (PP) population, moxonidine statistically significantly (p = 0.025) decreased the AUC for insulin from baseline in the PP population; for metformin, the treatment effect on insulin was a small, net increase resulting in a statistically significant between-group difference of 16.2% (95% CI = 0.1-35.0). The change in mean insulin AUC was most marked in the subgroup of patients with higher sympathetic activity (heart rate >80 bpm). Mean fasting plasma glucose (FPG) levels and HbA1c levels were largely unchanged by moxonidine treatment but significantly decreased by metformin treatment. The difference between the groups was 14.7% (p = 0.0523) in the intent-to-treat (ITT) sample. By study end, both treatments had significantly increased the Matsuda Insulin Sensitivity Index (ISI) from baseline to a comparable extent: moxonidine by reducing plasma insulin after a glucose challenge, metformin by reducing FPG. BMI fell significantly in both groups and blood pressure normalized; both drugs were well tolerated. Moxonidine improved insulin sensitivity in response to glucose challenge in patients with evidence of metabolic syndrome. This improvement resulted from a reduction in plasma insulin levels and was most marked in patients with high sympathetic drive at baseline. By enhancing insulin sensitivity, moxonidine treatment may help prevent the development of diabetes and thereby ameliorate the risk for cardiovascular disease.

135-Day Interventions of Yam Dioscorin and the Dipeptide Asn-Trp (NW) To Reduce Weight Gains and Improve Impaired Glucose Tolerances in High-Fat Diet-Induced C57BL/6 Mice.

PubMed

Wu, Guang-Cheng; Lin, Shyr-Yi; Liang, Hong-Jen; Hou, Wen-Chi

2018-01-24

The C57BL/6J mice were fed a 135-day normal diet or a high-fat diet (HFD) without, or concurrent with, a single yam dioscorin (80 mg/kg) or dipeptide NW (40 mg/kg) intervention every day. The final body weights (g) of mice were 26.1 ± 1.4, 34.97 ± 2.1, 31.75 ± 2.6, and 31.66 ± 3.1, respectively, for normal diet-fed, HFD-fed, dioscorin-intervened, and NW-intervened group. The mice in both intervened groups showed similar less weight gains and had significant differences (P < 0.05) compared to those in the HFD group under the same cumulative HFD intakes. The blood biochemical index of mice with dioscorin interventions showed significantly lower contents in total cholesterol and low-density lipoprotein, and NW interventions showed significantly lower total triglyceride contents compared to those of the HFD group (P < 0.05). Both intervened mice exhibited similar reductions in total visceral lipid contents and have significant differences compared to those of the HFD group (P < 0.05). The dioscorin intervention was better than NW interventions in lowering blood glucose levels by oral glucose tolerance tests and both showed significant differences (P < 0.05) compared to those in the HFD group. Yam dioscorin or dipeptide NW will potentially be used for preventive functional foods of less body weight gains and impaired glucose tolerance controls, which require further clinical trial investigations.

Improved growth and ethanol fermentation of Saccharomyces cerevisiae in the presence of acetic acid by overexpression of SET5 and PPR1.

PubMed

Zhang, Ming-Ming; Zhao, Xin-Qing; Cheng, Cheng; Bai, Feng-Wu

2015-12-01

To better understand the contribution of zinc-finger proteins to environmental stress tolerance, particularly inhibition from acetic acid, which is a potent inhibitor for cellulosic ethanol production by microbial fermentations, SET5 and PPR1 were overexpressed in Saccharomyces cerevisiae BY4741. With 5 g/L acetic acid addition, engineered strains BY4741/SET5 and BY4741/PPR1 showed improved growth and enhanced ethanol fermentation performance compared to that with the control strain. Similar results were also observed in ethanol production using corn stover hydrolysate. Further studies indicated that SET5 and PPR1 overexpression in S. cerevisiae significantly improved activities of antioxidant enzymes and ATP generation in the presence of acetic acid, and consequently decreased intracellular accumulation of reactive oxygen species (50.9 and 45.7%, respectively). These results revealed the novel functions of SET5 and PPR1 for the improvement of yeast acetic acid tolerance, and also implicated the involvement of these proteins in oxidative stress defense and energy metabolism in S. cerevisiae. This work also demonstrated that overexpression of SET5 and PPR1 would be a feasible strategy to increase cellulosic ethanol production efficiency. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mechanisms of Orthostatic Tolerance Improvement Following Artificial Gravity Exposure Differ Between Men and Women

NASA Technical Reports Server (NTRS)

Evans, J. M.; Stenger, M. B.; Ferguson, C. R.; Ribiero, L. C.; Zhang, Q.; Moore, F. B.; Serrador, J.; Smith, J. D.; Knapp, C. F.

2014-01-01

We recently determined that a short exposure to artificial gravity (AG) improved the orthostatic tolerance limit (OTL) of cardiovascularly deconditioned subjects. We now seek to determine the mechanisms of that improvement in these hypovolemic men and women. Methods. We determined the orthostatic tolerance limit (OTL) of 9 men and 8 women following a 90 min exposure to AG compared to 90 min of head down bed rest (HDBR). In both cases (21 days apart), subjects were made hypovolemic (low salt diet plus 20 mg intravenous furosemide). Orthostatic tolerance was determined from a combination of head up tilt and increasing lower body negative pressure until presyncope. Mean values and correlations with OTL were determined for heart rate, blood pressure, stroke volume, cardiac output and peripheral resistance (Finometer), cerebral artery blood velocity (DWL), partial pressure of carbon dioxide (Novametrics) and body segmental impedance (UFI THRIM) were measured during supine baseline, during OTL to presyncope and during supine recovery Results. Orthostatic tolerance of these hypovolemic subjects was significantly greater on the day of AG exposure than on the HDBR day. Regression of OTL on these variables identified significant relationships on the HDBR day that were not evident on the AG day: resting TPR correlated positively while resting cerebral flow correlated negatively with OTL. On both days, women's resting stroke volume correlated positively with orthostatic tolerance. Higher group mean values of stroke volume and cerebral artery flow and lower values of blood pressure, peripheral vascular and cerebrovascular resistance both at control and during OTL testing were observed on the AG day. Even though regression of OTL on resting stroke volume was significant only in women, presyncopal stroke volume reached the same level on each day of study for both men and women while the OTL test lasted 30% longer in men and 22% longer in women. Cerebral artery flow appeared to follow stroke volume and absolute values of cerebral flow did not correlate with the development of presyncope. Women responded to AG exposure with elevated cerebral flow at resting control and throughout the OTL test, implying a loss of autoregulation in deconditioned (hypovolemic) women following AG exposure. Conclusions. Before countermeasures to space flight cardiovascular deconditioning are established, gender differences in cardiovascular responses to orthostatic stress, in general, and to orthostatic stress following exposure to artificial gravity, in particular, need to be determined. Since, in both men and women, a single, acute bout of AG exposure improved orthostatic tolerance, the feasibility of short exposures to AG during longer spaceflights or prior to entry into a gravity (Earth or Mars) environment, should be explored. Given the known beneficial effects of AG on other organ systems, the present study indicates that the positive effects of AG on cardiac stroke volume make AG a likely candidate for maintaining cardiovascular conditioning.

Engineering microbes for tolerance to next-generation biofuels

PubMed Central

2011-01-01

A major challenge when using microorganisms to produce bulk chemicals such as biofuels is that the production targets are often toxic to cells. Many biofuels are known to reduce cell viability through damage to the cell membrane and interference with essential physiological processes. Therefore, cells must trade off biofuel production and survival, reducing potential yields. Recently, there have been several efforts towards engineering strains for biofuel tolerance. Promising methods include engineering biofuel export systems, heat shock proteins, membrane modifications, more general stress responses, and approaches that integrate multiple tolerance strategies. In addition, in situ recovery methods and media supplements can help to ease the burden of end-product toxicity and may be used in combination with genetic approaches. Recent advances in systems and synthetic biology provide a framework for tolerance engineering. This review highlights recent targeted approaches towards improving microbial tolerance to next-generation biofuels with a particular emphasis on strategies that will improve production. PMID:21936941

Maghemite Nanoparticles Acts as Nanozymes, Improving Growth and Abiotic Stress Tolerance in Brassica napus

NASA Astrophysics Data System (ADS)

Palmqvist, N. G. Martin; Seisenbaeva, Gulaim A.; Svedlindh, Peter; Kessler, Vadim G.

2017-12-01

Yttrium doping-stabilized γ-Fe2O3 nanoparticles were studied for its potential to serve as a plant fertilizer and, through enzymatic activity, support drought stress management. Levels of both hydrogen peroxide and lipid peroxidation, after drought, were reduced when γ-Fe2O3 nanoparticles were delivered by irrigation in a nutrient solution to Brassica napus plants grown in soil. Hydrogen peroxide was reduced from 151 to 83 μM g-1 compared to control, and the malondialdehyde formation was reduced from 36 to 26 mM g-1. Growth rate of leaves was enhanced from 33 to 50% growth compared to fully fertilized plants and SPAD-measurements of chlorophyll increased from 47 to 52 suggesting improved agronomic properties by use of γ-Fe2O3 nanoparticles as fertilizer as compared to chelated iron.

Establishing the tolerability and performance of tamarind seed polysaccharide (TSP) in treating dry eye syndrome: results of a clinical study.

PubMed

Rolando, Maurizio; Valente, Cristiana

2007-03-29

One of the problems arising from available preparations for dry eye syndrome is the limited residence time of products on the ocular surface. In this paper, we look at an innovative new treatment for dry eye, tamarind seed polysaccharide (TSP). TSP possesses mucomimetic, mucoadhesive and pseudoplastic properties. The 'mucin-like' molecular structure of TSP is similar to corneal and conjunctival mucin 1 (MUC1), a transmembrane glycoprotein thought to play an essential role in protecting and wetting the corneal surface and may explain its increased retention on the eye surface. The activity of TSP and hyaluronic acid (HA) in the treatment of dry eye syndrome was compared in an open-label, randomised, single-centre clinical study. Thirty patients were randomised to receive three or more applications per day of either TSP 0.5%, TSP 1% or HA 0.2% (Hyalistiltrade mark) over a period of 90 days. The primary objective of tolerability was assessed by visual analogue scale (VAS), scoring of specific symptoms and the incidence of adverse events. Secondary objectives included improvement in stability of the precorneal tear film, subjective symptoms and corneal and conjunctival staining. TSP 0.5% and 1% were comparable to HA 0.2% with regard to both primary and secondary objective parameters.TSP 1% showed benefits over HA 0.2% for the subjective symptoms; trouble blinking, ocular burning and foreign body sensation. This study suggests that TSP 0.5% and 1% offer at least equivalent relief to HA 0.2% for dry eye syndrome. All treatments demonstrated optimal tolerability and are suitable for frequent use in the therapy of dry eye.TSP 1% produced promising results in terms of improvements in certain patient symptoms and suggests benefits of the TSP formulation. This study paves the way for a larger study to further establish the performance and safety of TSP compared with HA and highlights the need to expand this therapeutic agent to a wider dry eye population.

The mechanism of diabetes control after gastrointestinal bypass surgery reveals a role of the proximal small intestine in the pathophysiology of type 2 diabetes.

PubMed

Rubino, Francesco; Forgione, Antonello; Cummings, David E; Vix, Michel; Gnuli, Donatella; Mingrone, Geltrude; Castagneto, Marco; Marescaux, Jacques

2006-11-01

Most patients who undergo Roux-en-Y gastric bypass (RYGB) experience rapid resolution of type 2 diabetes. Prior studies indicate that this results from more than gastric restriction and weight loss, implicating the rearranged intestine as a primary mediator. It is unclear, however, if diabetes improves because of enhanced delivery of nutrients to the distal intestine and increased secretion of hindgut signals that improve glucose homeostasis, or because of altered signals from the excluded segment of proximal intestine. We sought to distinguish between these two mechanisms. Goto-Kakizaki (GK) type 2 diabetic rats underwent duodenal-jejunal bypass (DJB), a stomach-preserving RYGB that excludes the proximal intestine, or a gastrojejunostomy (GJ), which creates a shortcut for ingested nutrients without bypassing any intestine. Controls were pair-fed (PF) sham-operated and untreated GK rats. Rats that had undergone GJ were then reoperated to exclude the proximal intestine; and conversely, duodenal passage was restored in rats that had undergone DJB. Oral glucose tolerance (OGTT), food intake, body weight, and intestinal nutrient absorption were measured. There were no differences in food intake, body weight, or nutrient absorption among surgical groups. DJB-treated rats had markedly better oral glucose tolerance compared with all control groups as shown by lower peak and area-under-the-curve glucose values (P < 0.001 for both). GJ did not affect glucose homeostasis, but exclusion of duodenal nutrient passage in reoperated GJ rats significantly improved glucose tolerance. Conversely, restoration of duodenal passage in DJB rats reestablished impaired glucose tolerance. This study shows that bypassing a short segment of proximal intestine directly ameliorates type 2 diabetes, independently of effects on food intake, body weight, malabsorption, or nutrient delivery to the hindgut. These findings suggest that a proximal intestinal bypass could be considered for diabetes treatment and that potentially undiscovered factors from the proximal bowel might contribute to the pathophysiology of type 2 diabetes.

Stress Inducible Expression of AtDREB1A Transcription Factor in Transgenic Peanut (Arachis hypogaea L.) Conferred Tolerance to Soil-Moisture Deficit Stress

PubMed Central

Sarkar, Tanmoy; Thankappan, Radhakrishnan; Kumar, Abhay; Mishra, Gyan P.; Dobaria, Jentilal R.

2016-01-01

Peanut, an important oilseed crop, is gaining priority for the development of drought tolerant genotypes in recent times, since the area under drought is constantly on the rise. To achieve this, one of the important strategies is to genetically engineer the ruling peanut varieties using transcription factor regulating the expression of several downstream, abiotic-stress responsive gene(s). In this study, eight independent transgenic peanut (cv. GG20) lines were developed using AtDREB1A gene, encoding for a transcription factor, through Agrobacterium-mediated genetic transformation. The transgene insertion was confirmed in (T0) using PCR and Dot-blot analysis, while copy-number(s) was ascertained using Southern-blot analysis. The inheritance of AtDREB1A gene in individual transgenic plants (T1 and T2) was confirmed using PCR. In homozygous transgenic plants (T2), under soil-moisture deficit stress, elevated level of AtDREB1A transgene expression was observed by RT-PCR assay. The transgenic plants at 45-d or reproductive growth stage showed tolerance to severe soil-moisture deficit stress. Physio-biochemical parameters such as proline content, osmotic potential, relative water content, electrolytic leakage, and total-chlorophyll content were found positively correlated with growth-related traits without any morphological abnormality, when compared to wild-type. qPCR analysis revealed consistent increase in expression of AtDREB1A gene under progressive soil-moisture deficit stress in two homozygous transgenic plants. The transgene expression showed significant correlation with improved physio-biochemical traits. The improvement of drought-stress tolerance in combination with improved growth-related traits is very essential criterion for a premium peanut cultivar like GG20, so that marginal farmers of India can incur the economic benefits during seasonal drought and water scarcity. PMID:27446163

Glycine betaine improves oxidative stress tolerance and biocontrol efficacy of antagonistic yeast Cystofilobasidium infirmominiatum

USDA-ARS?s Scientific Manuscript database

The effect of H2O2-induced oxidative stress on the viability of the yeast antagonist, Cystofilobasidium infirmominiatum, as well as the effect of exogenous glycine betaine (GB) on yeast viability under oxidative stress, was determined. GB treatment improved the tolerance of C. infirmominiatum to ox...

Cool-season annual grasses interseeded into bermudagrass with improved cold-tolerance for grazing in the upper south

USDA-ARS?s Scientific Manuscript database

Bermudagrass [Cynodon dactylon (Pers.) L.] cultivars with improved cold tolerance can be utilized for grazing in the transition zone between the temperate northeast and subtropical southeast, but these bermudagrasses generally do not provide adequate growth for stocking until late May to early June....

Expression of an Arabidopsis sodium/proton antiporter gene (AtNHX1)in peanut to improve salt tolerance

USDA-ARS?s Scientific Manuscript database

Salinity is a major environmental stress that affects agricultural productivity worldwide. One approach to improving salt tolerance in crops is through high expression of the Arabidopsis gene AtNHX1, which encodes a vacuolar sodium/proton antiporter that sequesters excess sodium ion into the large i...

Tolerability of extended-release quetiapine fumarate compared with immediate-release quetiapine fumarate in older patients with Alzheimer's disease with symptoms of psychosis and/or agitation: a randomised, double-blind, parallel-group study.

PubMed

De Deyn, Peter Paul; Eriksson, Hans; Svensson, Hanna

2012-03-01

The objective of this study was to assess the safety and tolerability of extended-release quetiapine fumarate (quetiapine XR) compared with quetiapine immediate-release (quetiapine IR) in older patients with Alzheimer's disease with symptoms of psychosis and/or agitation. This was a 6-week, double-blind, double-dummy, randomised study. Of the 109 patients screened, 100 were randomised to receive quetiapine XR (n = 68) or quetiapine IR (n = 32), at doses of 50 and 25 mg/day, respectively. Treatment was escalated to 100 mg/day by Day 4. At Day 8, a flexible-dose (50-300 mg/day) period began when dose adjustment was made at the investigator's discretion. The primary variable was incidence and type of adverse events (AEs). Secondary variables included efficacy and other safety assessments. Mean daily doses were 143.6 and 142.0 mg in the quetiapine XR and quetiapine IR groups, respectively. Ninety patients completed the study; only one withdrew (in the quetiapine XR group) because of an AE. Laboratory evaluations identified severe neutropaenia (one patient), mild neutropaenia (three patients) and eosinophilia (five patients); however, these were not reported, as AEs and confounding factors, such as patient age, concomitant illness and medication, made it difficult to determine any relationship to quetiapine treatment. Numerical improvements from baseline were seen across both treatment groups in Neuropsychiatric Inventory frequency × severity total, Neuropsychiatric Inventory-Nursing Home version, Cohen-Mansfield Agitation Inventory, Clinical Global Impression-Severity of Illness and Clinical Global Impression-Improvement scores. Quetiapine XR dosed up to 300 mg/day was generally well tolerated, with a similar profile to that of quetiapine IR. Copyright © 2011 John Wiley & Sons, Ltd.

XeCl excimer laser with new prism resonator configurations and its performance characteristics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Benerji, N. S., E-mail: nsb@rrcat.gov.in, E-mail: bsingh@rrcat.gov.in; Singh, A.; Varshnay, N.

2015-07-15

New resonator cavity configurations, namely, the prism resonator and unstable prism resonator, are demonstrated for the first time in an excimer (XeCl) laser with interesting and novel results. High misalignment tolerance ∼50 mrad is achieved with considerably reduced beam divergence of less than ∼1 mrad without reduction in output power capabilities of the laser. The misalignment tolerance of ∼50 mrad is a dramatic improvement of ∼25 times compared to ∼2 mrad normally observed in standard excimer laser with plane-plane cavity. Increase in depth of focus from 3 mm to 5.5 mm was also achieved in case of prism resonator configurationmore » with an improvement of about 60%. Unstable prism resonator configuration is demonstrated here in this paper with further reduction in beam divergence to about 0.5 mrad using plano-convex lens as output coupler. The misalignment tolerance in case of unstable prism resonator was retained at about 30 mrad which is a high value compared to standard unstable resonators. The output beam spot was completely filled with flat-top profile with prism resonator configurations, which is desired for various material processing applications. Focusing properties and beam divergence in case of prism resonator have been investigated using SEM (scanning electron microscope) images. SEM images of the focused spot size (∼20 μm holes) on metal sheet indicate beam divergence of about 0.05 mrad which is about 1.5 times diffraction limit. Energy contained in this angle is thus sufficient for micro-machining applications. Clean and sharp edges of the micro-holes show high pointing stability with multiple shot exposures. Such characteristics of the excimer laser system will be extremely useful in micro-machining and other field applications.« less

XeCl excimer laser with new prism resonator configurations and its performance characteristics.

PubMed

Benerji, N S; Singh, A; Varshnay, N; Singh, Bijendra

2015-07-01

New resonator cavity configurations, namely, the prism resonator and unstable prism resonator, are demonstrated for the first time in an excimer (XeCl) laser with interesting and novel results. High misalignment tolerance ∼50 mrad is achieved with considerably reduced beam divergence of less than ∼1 mrad without reduction in output power capabilities of the laser. The misalignment tolerance of ∼50 mrad is a dramatic improvement of ∼25 times compared to ∼2 mrad normally observed in standard excimer laser with plane-plane cavity. Increase in depth of focus from 3 mm to 5.5 mm was also achieved in case of prism resonator configuration with an improvement of about 60%. Unstable prism resonator configuration is demonstrated here in this paper with further reduction in beam divergence to about 0.5 mrad using plano-convex lens as output coupler. The misalignment tolerance in case of unstable prism resonator was retained at about 30 mrad which is a high value compared to standard unstable resonators. The output beam spot was completely filled with flat-top profile with prism resonator configurations, which is desired for various material processing applications. Focusing properties and beam divergence in case of prism resonator have been investigated using SEM (scanning electron microscope) images. SEM images of the focused spot size (∼20 μm holes) on metal sheet indicate beam divergence of about 0.05 mrad which is about 1.5 times diffraction limit. Energy contained in this angle is thus sufficient for micro-machining applications. Clean and sharp edges of the micro-holes show high pointing stability with multiple shot exposures. Such characteristics of the excimer laser system will be extremely useful in micro-machining and other field applications.

Magnetic Resonance Imaging-Guided, Open-Label, High-Frequency Repetitive Transcranial Magnetic Stimulation for Adolescents with Major Depressive Disorder.

PubMed

Wall, Christopher A; Croarkin, Paul E; Maroney-Smith, Mandie J; Haugen, Laura M; Baruth, Joshua M; Frye, Mark A; Sampson, Shirlene M; Port, John D

2016-09-01

Preliminary studies suggest that repetitive transcranial magnetic stimulation (rTMS) may be an effective and tolerable intervention for adolescents with treatment-resistant depression. There is limited rationale to inform coil placement for rTMS dosing in this population. We sought to examine and compare three localization techniques for coil placement in the context of an open-label trial of high-frequency rTMS for adolescents with treatment-resistant depression. Ten adolescents with treatment-resistant depression were enrolled in an open-label trial of high-frequency rTMS. Participants were offered 30 rTMS sessions (10 Hz, 120% motor threshold, left 3000 pulses applied to the dorsolateral prefrontal cortex) over 6-8 weeks. Coil placement for treatment was MRI guided. The scalp location for treatment was compared with the locations identified with standard 5 cm rule and Beam F3 methods. Seven adolescents completed 30 rTMS sessions. No safety or tolerability concerns were identified. Depression severity as assessed with the Children's Depression Rating Scale Revised improved from baseline to treatment 10, treatment 20, and treatment 30. Gains in depressive symptom improvement were maintained at 6 month follow-up visits. An MRI-guided approach for coil localization was feasible and efficient. Our results suggest that the 5 cm rule, Beam F3, and the MRI-guided localization approaches provided variable scalp targets for rTMS treatment. Open-label, high-frequency rTMS was feasible, tolerable, and effective for adolescents with treatment-resistant depression. Larger, blinded, sham-controlled trials are needed for definitive safety and efficacy data. Further efforts to understand optimal delivery, dosing, and biomarker development for rTMS treatments of adolescent depression are warranted.

An Open Label Clinical Trial to Evaluate the Efficacy and Tolerance of a Retinol and Vitamin C Facial Regimen in Women With Mild-to-Moderate Hyperpigmentation and Photodamaged Facial Skin.

PubMed

Herndon, James H; Jiang, Lily I; Kononov, Tatiana; Fox, Theresa

2016-04-01

A 12-week open-label, single-center clinical usage trial was conducted to determine the effectiveness of a dual product regimen consisting of a 0.5% retinol treatment and an anti-aging moisturizer with 30% vitamin C in women with mild to moderate hyperpigmented and photodamaged facial skin. Clinical grading of several efficacy parameters, tolerability evaluations, subject self-assessment questionnaires, and digital photography were completed at baseline and at weeks 4, 8, and 12. A total of 44 women completed the study. Effective ingredients incorporated into the 0.5% retinol treatment included encapsulated retinol for a retinol concentration of 0.5%, bakuchiol, and Ophiopogon japonicus root extract. The anti-aging moisturizer with 30% vitamin C contained 30% vitamin C in the form of tetrahexyldecyl ascorbate (THD ascorbate), alpha-tocopheryl acetate (vitamin E) and ubiquinone (coenzyme Q10). The facial regimen produced a statistically significant decrease (improvement) in clinical grading scores for all parameters assessed at weeks 8 and 12 when compared with baseline scores. In addition, the majority of these parameters were improved at week 4. The test regimen was well-perceived by the subjects for various inquiries regarding facial skin condition, product efficacy, and product attributes. Several tolerability parameters were assessed with no statistically significant increase except for dryness. A statistically significant increase in clinical grading scores for dryness on the face occurred at weeks 4 and 8 when compared to baseline scores. The increase in dryness is expected when introducing a retinol product to a facial regimen and the dryness did not persist to the week 12 time point.

Improvement of Glucose Metabolism in Patients with Impaired Glucose Tolerance or Diabetes by Long-Term Administration of a Palatinose-Based Liquid Formula as a Part of Breakfast

PubMed Central

Sakuma, Masae; Arai, Hidekazu; Mizuno, Akira; Fukaya, Makiko; Matsuura, Motoi; Sasaki, Hajime; Yamanaka-Okumura, Hisami; Yamamoto, Hironori; Taketani, Yutaka; Doi, Toshio; Takeda, Eiji

2009-01-01

A palatinose-based liquid formula (palatinose-formula), suppresses postprandial plasma glucose and insulin levels in healthy men. The objective of this study was to investigate the effects of long-term palatinose-formula ingestion on glucose metabolism in patients with impaired glucose tolerance (IGT) or type 2 diabetes. Two patients with IGT and 7 patients with type 2 diabetes participated in the palatinose-formula and dextrin-based liquid formula (dextrin-formula) loading test and long-term palatinose-formula administration study. After a 3-month control period, palatinose-formula (1046 kJ) was ingested daily by patients as a part of breakfast for 5 months. In the loading test, palatinose-formula suppressed postprandial plasma glucose and insulin levels and areas under the curve compared with those after dextrin-formula ingestion. In the long-term study, glycated hemoglobin levels (after 3 months and 5 months of treatment) and serum 8-hydroxydeoxyguanosine levels (after 5 months of treatment) were markedly decreased comparing with those at baseline. Intake of 1046 kJ palatinose-formula as a part of breakfast over a long-term period may be effective for improvement of glucose metabolism in patients with IGT or type 2 diabetes. PMID:19794923

Chromosome-anchored QTL conferring aluminum tolerance in hexaploid oat

USDA-ARS?s Scientific Manuscript database

Abstract Aluminum (Al) toxicity is a major constraint on crop production in acid soils around the world. Hexaploid oat (Avena sativa L.) possesses signi'cant Al tolerance making it a good candidate for production in these environments. Genetic improvement for Al tolerance in oat has traditionally be...

Clinical evaluation of a nutraceutical, carprofen and meloxicam for the treatment of dogs with osteoarthritis.

PubMed

Moreau, M; Dupuis, J; Bonneau, N H; Desnoyers, M

2003-03-15

The efficacy, tolerance and ease of administration of a nutraceutical, carprofen or meloxicam were evaluated in a prospective, double-blind study on 71 dogs with osteoarthritis. The client-owned dogs were randomly assigned to one of the three treatments or to a placebo control group. The influence of osteoarthritis on the dogs' gait was described by comparing the ground reaction forces of the arthritic dogs and 10 normal dogs. Before the treatments began, and 30 and 60 days later, measurements were made of haematological and biochemical variables and of the ground reaction forces of the arthritic limb, and subjective assessments were made by the owners and by the orthopaedic surgeons. Changes in the ground reaction forces were specific to the arthritic joint, and were significantly improved by carprofen and meloxicam but not by the nutraceutical; the values returned to normal only with meloxicam. The orthopaedic surgeons assessed that there had been an improvement with carprofen and meloxicam, but the owners considered that there had been an improvement only with meloxicam. The blood and faecal analyses did not reveal any changes. The treatments were well tolerated, except for a case of hepatopathy in a dog treated with carprofen.

Graded Aerobic Treadmill Testing in Adolescent Traumatic Brain Injury Patients.

PubMed

Cordingley, Dean M; Girardin, Richard; Morissette, Marc P; Reimer, Karen; Leiter, Jeff; Russell, Kelly; Ellis, Michael J

2017-11-01

To examine the safety and tolerability of clinical graded aerobic treadmill testing in recovering adolescent moderate and severe traumatic brain injury (TBI) patients referred to a multidisciplinary pediatric concussion program. We completed a retrospective case series of two moderate and five severe TBI patients (mean age, 17.3 years) who underwent initial Buffalo Concussion Treadmill Testing at a mean time of 71.6 days (range, 55-87) postinjury. Six patients completed one graded aerobic treadmill test each and one patient underwent initial and repeat testing. There were no complications. Five initial treadmill tests were completely tolerated and allowed an accurate assessment of exercise tolerance. Two initial tests were terminated early by the treatment team because of neurological and cardiorespiratory limitations. As a result of testing, two patients were cleared for aerobic exercise as tolerated and four patients were treated with individually tailored submaximal aerobic exercise programs resulting in subjective improvement in residual symptoms and/or exercise tolerance. Repeat treadmill testing in one patient performed after 1 month of treatment with submaximal aerobic exercise prescription was suggestive of improved exercise tolerance. One patient was able to tolerate aerobic exercise following surgery for posterior glottic stenosis. Preliminary results suggest that graded aerobic treadmill testing is a safe, well tolerated, and clinically useful tool to assess exercise tolerance in appropriately selected adolescent patients with TBI. Future prospective studies are needed to evaluate the effect of tailored submaximal aerobic exercise prescription on exercise tolerance and patient outcomes in recovering adolescent moderate and severe TBI patients.

Oxymetazoline plus dexpanthenol in nasal congestion.

PubMed

Jagade, Mohan V; Langade, Deepak G; Pophale, Rupesh R; Prabhu, Arun

2008-12-01

To compare the efficacy and tolerability of Oxymetazoline 0.05 % plus Dexpanthanol 5% versus Xylometazoline 0.1 % nasal drops in patients with nasal congestion due to allergic rhinitis and following nasal surgery. An investigator-blind, randomized, controlled, phase IV clinical trial conducted in 100 patients with acute allergic rhinitis or patients post-nasal surgery. Patients received either Oxymetazoline 0.05% with Dexpanthanol 5% (OD) or Xylometazoline 0.1% (XO) nasal drops. Relief from nasal congestion was significantly better in the OD group then in the XO group (mean nasal scores 1.24 vs 1.86). Significantly more improvement in sneezing and decrease in nasal discharge was seen in the OD group than the XO group. Nasal irritation in the OD group was significantly less as compared to XO group (0.38 v/s 1.12 on second day and 0.10 vs 0.36 on the fourth day). The recovery time for OD group was 1.08 hours, which was significantly (46 min) lesser than that of the XO group. Rebound congestion was significantly less in OD as compared to XO group (6.25% vs 82.98%). 93.75% of the physicians in the OD group and 51.28% in XO group reported response to therapy as good to excellent. 95.83% patients in the OD group and only 52.91% patients in the XO group rated tolerability to therapy as good to excellent. Oxymetazoline and dexpanthenol combination has a better efficacy, shorter recovery time, causes lesser rebound congestion and has better tolerability than xylometazoline.

Light induced intraspecific variability in response to thermal stress in the hard coral Stylophora pistillata

PubMed Central

Wijgerde, Tim; Dini-Andreote, Francisco; Eriksson, Britas Klemens; Salles, Joana Falcão; Pen, Ido; Wild, Christian

2017-01-01

Recent research suggests that prior exposure of several months to elevated irradiance induces enhanced thermal tolerance in scleractinian corals. While this tolerance has been reported at the species level, individual coral colonies may react differently due to individual variability in thermal tolerance. As thermal anomalies are predicted to become common in the upcoming future, intraspecific variation may be key to the survival of coral populations. In order to study light-history based thermal stress responses on individual colonies, we developed a preliminary microcosm experiment where three randomly chosen, aquacultured colonies of the model coral Stylophora pistillata were exposed to two irradiance treatments (200 and 400 μmol photons m−2 s−1) for 31 days, followed by artificially induced heat stress (∼33.4 °C). We found different responses to occur at both the intraspecific and the intracolonial levels, as indicated by either equal, less severe, delayed, and/or even non-necrotic responses of corals previously exposed to the irradiance of 400 compared to 200 μmol photons m−2 s−1. In addition, all individual colonies revealed light-enhanced calcification. Finally, elevated irradiance resulted in a lower chlorophyll a concentration in one colony compared to the control treatment, and the same colony displayed more rapid bleaching compared to the other ones. Taken together, this study highlights the potential importance of intra-individual variability in physiological responses of scleractinian corals and provides recommendations for improving methodological designs for future studies. PMID:29038747

Pyridostigmine in the treatment of postural orthostatic tachycardia: a single-center experience.

PubMed

Kanjwal, Khalil; Karabin, Beverly; Sheikh, Mujeeb; Elmer, Lawrence; Kanjwal, Yousuf; Saeed, Bilal; Grubb, Blair P

2011-06-01

The long-term efficacy of pyridostigmine, a reversible acetyl cholinesterase inhibitor, in the treatment of postural orthostatic tachycardia syndrome (POTS) patients remains unclear. We report our retrospective, single-center, long-term experience regarding the efficacy and adverse effect profile of pyridostigmine in the treatment of POTS patients. This retrospective study included an extensive review of electronic charts and data collection in regards to patient demographics, orthostatic parameters, side-effect profile, subjective response to therapy, as well as laboratory studies recorded at each follow-up visit to our institution's Syncope and Autonomic Disorders Center. The response to pyridostigmine therapy was considered successful if patient had both symptom relief in addition to an objective response in orthostatic hemodynamic parameters (heart rate [HR] and blood pressure). Three hundred patients with POTS were screened for evaluation in this study. Of these 300, 203 patients with POTS who received pyridostigmine therapy were reviewed. Of these 203 patients, 168 were able to tolerate the medication after careful dose titration. The mean follow-up duration in this group of patients was 12 ± 3 (9-15) months. Pyridostigmine improved symptoms of orthostatic intolerance in 88 of 203 (43%) of total patients or 88 of 172 (51%) who were able to tolerate the drug. The symptoms that improved the most included fatigue (55%), palpitations (60%), presyncope (60%), and syncope (48%). Symptom reduction correlated with a statistically significant improvement in upright HR and diastolic blood pressure after treatment with pyridostigmine as compared to their baseline hemodynamic parameters (standing HR 94 ± 19 vs 82 ± 16, P < 0.003, standing diastolic blood pressure 71 ± 11 vs 74 ± 12, P < 0.02). Gastrointestinal problems were the most common adverse effects (n = 39, 19%) reported. The overall efficacy of pyridostigmine in our study was seen in 42% of total patients or 52% of patients who could tolerate taking the drug. The subgroup of POTS patients who can tolerate oral pyridostigmine may demonstrate improvement in their standing HR, standing diastolic blood pressure, and clinical symptoms of orthostatic intolerance. ©2011, The Authors. Journal compilation ©2011 Wiley Periodicals, Inc.

An experimental analysis of acquired impulse control among adult humans intolerant to alcohol

PubMed Central

Wang, Jianxin; Rao, Yulei; Houser, Daniel E.

2017-01-01

The ability to control tempting impulses impacts health, education, and general socioeconomic outcomes among people at all ages. Consequently, whether and how impulse control develops in adult populations is a topic of enduring interest. Although past research has shed important light on this question using controlled intervention studies, here we take advantage of a natural experiment in China, where males but not females encounter substantial social pressure to consume alcohol. One-third of our sample, all of whom are Han Chinese, is intolerant to alcohol, whereas the remaining control sample is observationally identical but alcohol tolerant. Consistent with previous literature, we find that intolerant males are significantly more likely to exercise willpower to limit their alcohol consumption than alcohol-tolerant males. In view of the strength model of self-control, we hypothesize that this enables improved impulse control in other contexts as well. To investigate this hypothesis, we compare decisions in laboratory games of self-control between the tolerant and intolerant groups. We find that males intolerant to alcohol and who regularly encounter drinking environments control their selfish impulses significantly better than their tolerant counterparts. On the other hand, we find that female Han Chinese intolerant to alcohol do not use self-control to limit alcohol consumption more than tolerant females, nor do the tolerant and intolerant females exhibit differences in self-control behaviors. Our research indicates that impulse control can be developed in adult populations as a result of self-control behaviors in natural environments, and shows that this skill has generalizable benefits across behavioral domains. PMID:28119501

Transient improvement after brief antiepileptic drug withdrawal in the epilepsy monitoring unit--possible relationship to AED tolerance.

PubMed

Azar, Nabil J; Lagrange, Andre H; Wang, Lily; Song, Yanna; Abou-Khalil, Bassel W

2010-05-01

A drug holiday seems to produce seizure interval prolongation (SIP) after reinstitution of antiepileptic drugs (AEDs). This effect was demonstrated mainly with carbamazepine. We evaluated SIP with newer AEDs and tested the relationship of SIP to history of AED tolerance. We prospectively studied patients with refractory epilepsy admitted to the Vanderbilt epilepsy monitoring unit (EMU) over a period of 12 months. We included only patients on levetiracetam, lamotrigine, or oxcarbazepine who had their AEDs withdrawn on admission and reinstituted without change upon discharge. We defined SIP as the interval from EMU discharge to first seizure minus the interval between the last two seizures before EMU admission. A total of 43 patients completed the study; 15 were on monotherapy. SIP was greater than zero in this patient group (p < 0.0001), with a mean prolongation of 19.4 +/- 28.0 days. The average SIP was higher (p = 0.01) in patients on monotherapy (29.7 +/- 23.8 days) than patients on polytherapy (13.9 +/- 29.0 days). SIP tended to be greater in patients with a prior history of AED tolerance (25.7 +/- 36.8 days) compared to patient with no prior history of AED tolerance (14.0 +/- 16.3 days). SIP does occur after brief AED withdrawal. This effect is greater in patients on monotherapy and tends to be larger in patients with a history of AED tolerance. The SIP effect may be related to the phenomenon of tolerance, clinically seen as resistance to AED therapeutic effect.

Gait planning for a quadruped robot with one faulty actuator

NASA Astrophysics Data System (ADS)

Chen, Xianbao; Gao, Feng; Qi, Chenkun; Tian, Xinghua

2015-01-01

Fault tolerance is essential for quadruped robots when they work in remote areas or hazardous environments. Many fault-tolerant gaits planning method proposed in the past decade constrained more degrees of freedom(DOFs) of a robot than necessary. Thus a novel method to realize the fault-tolerant walking is proposed. The mobility of the robot is analyzed first by using the screw theory. The result shows that the translation of the center of body(CoB) can be kept with one faulty actuator if the rotations of the body are controlled. Thus the DOFs of the robot body are divided into two parts: the translation of the CoB and the rotation of the body. The kinematic model of the whole robot is built, the algorithm is developed to actively control the body orientations at the velocity level so that the planned CoB trajectory can be realized in spite of the constraint of the faulty actuator. This gait has a similar generation sequence with the normal gait and can be applied to the robot at any position. Simulations and experiments of the fault-tolerant gait with one faulty actuator are carried out. The CoB errors and the body rotation angles are measured. Comparing to the traditional fault-tolerant gait they can be reduced by at least 50%. A fault-tolerant gait planning algorithm is presented, which not only realizes the walking of a quadruped robot with a faulty actuator, but also efficiently improves the walking performances by taking full advantage of the remaining operational actuators according to the results of the simulations and experiments.

Metabolite profiling during cold acclimation of Lolium perenne genotypes distinct in the level of frost tolerance.

PubMed

Bocian, Aleksandra; Zwierzykowski, Zbigniew; Rapacz, Marcin; Koczyk, Grzegorz; Ciesiołka, Danuta; Kosmala, Arkadiusz

2015-11-01

Abiotic stresses, including low temperature, can significantly reduce plant yielding. The knowledge on the molecular basis of stress tolerance could help to improve its level in species of relatively high importance to agriculture. Unfortunately, the complex research performed so far mainly on model species and also, to some extent, on cereals does not fully cover the demands of other agricultural plants of temperate climate, including forage grasses. Two Lolium perenne (perennial ryegrass) genotypes with contrasting levels of frost tolerance, the high frost tolerant (HFT) and the low frost tolerant (LFT) genotypes, were selected for comparative metabolomic research. The work focused on the analysis of leaf metabolite accumulation before and after seven separate time points of cold acclimation. Gas chromatography-mass spectrometry (GC/MS) was used to identify amino acids (alanine, proline, glycine, glutamic and aspartic acid, serine, lysine and asparagine), carbohydrates (fructose, glucose, sucrose, raffinose and trehalose) and their derivatives (mannitol, sorbitol and inositol) accumulated in leaves in low temperature. The observed differences in the level of frost tolerance between the analysed genotypes could be partially due to the time point of cold acclimation at which the accumulation level of crucial metabolite started to increase. In the HFT genotype, earlier accumulation was observed for proline and asparagine. The increased amounts of alanine, glutamic and aspartic acids, and asparagine during cold acclimation could be involved in the regulation of photosynthesis intensity in L. perenne. Among the analysed carbohydrates, only raffinose revealed a significant association with the acclimation process in this species.

An experimental analysis of acquired impulse control among adult humans intolerant to alcohol.

PubMed

Wang, Jianxin; Rao, Yulei; Houser, Daniel E

2017-02-07

The ability to control tempting impulses impacts health, education, and general socioeconomic outcomes among people at all ages. Consequently, whether and how impulse control develops in adult populations is a topic of enduring interest. Although past research has shed important light on this question using controlled intervention studies, here we take advantage of a natural experiment in China, where males but not females encounter substantial social pressure to consume alcohol. One-third of our sample, all of whom are Han Chinese, is intolerant to alcohol, whereas the remaining control sample is observationally identical but alcohol tolerant. Consistent with previous literature, we find that intolerant males are significantly more likely to exercise willpower to limit their alcohol consumption than alcohol-tolerant males. In view of the strength model of self-control, we hypothesize that this enables improved impulse control in other contexts as well. To investigate this hypothesis, we compare decisions in laboratory games of self-control between the tolerant and intolerant groups. We find that males intolerant to alcohol and who regularly encounter drinking environments control their selfish impulses significantly better than their tolerant counterparts. On the other hand, we find that female Han Chinese intolerant to alcohol do not use self-control to limit alcohol consumption more than tolerant females, nor do the tolerant and intolerant females exhibit differences in self-control behaviors. Our research indicates that impulse control can be developed in adult populations as a result of self-control behaviors in natural environments, and shows that this skill has generalizable benefits across behavioral domains.

[Study of tolerance and aceptability of a hyperproteic enteral formula enriched in fiber].

PubMed

De Luis, Daniel Antonio; Izaola, Olatz; Castro, A; Martin, M; Torres, B; Lopez Gomez, Jj; Gomez Hoyos, E; Blanco Naveira, Mercedes

2014-10-18

To evaluate the gastrointestinal tolerance and acceptance of the new formulation of Isosource Protein ® Fibre® with a new blend of fibers IS50®. Opened, non-comparative, nonrandomized, descriptive study in patients requiring full enteral tube feeding for at least 7 days. Gastrointestinal tolerance was assessed by daily record of subjective gastrointestinal symptoms by the patient, and objectives behind the abdominal exploration by the researcher for up to 15 days. 18 patients were included with a mean age of 67.32 ± 13.8 years, of whom 66.7% were male. The average actual weight of the sample was 68.7 ± 9.8 kg (range: 51-90 kg) and BMI 24.0 ± 4.0 kg/m2 (range: 16.0 to 32.00 kg/m2). The average volume prescribed Isosource Protein® Fiber® was 1580 ± 282.7 ml / day (range: 1200 to 2000 ml/day). 72.22% of the patients received 1500 ml/day, received 16.67% 1750 ml / day, 5.56% received 2000 ml/day and 5.56% received 2500 ml/day. The analysis of the gastrointestinal tolerance of patients revealed that in the first study visit, reported no significant gastrointestinal problems, only one patient indicated the presence of mild constipation. By contrast, in the last study visit, it was observed that two patients reported constipation (mild to moderate) and two patients reported diarrhea (mild and severe). As for the evaluation of gastrointestinal tolerance by the investigator and depositional habit, the results show that in 100% cases tolerance was normal. Regarding the depositional habit, it was observed than the 66.7% of patients had no bowel movements at baseline, compared to 33.4% at the last visit of the patient (p = 0.035). In this sense, a significant increase (p = 0.035) in the mean number of daily bowel movements at the final visit (0.89 ± 0.90, range: 0-3) was observed, compared to the initial visit (0.44 ± 0.78, range: 0-3). Isosource Protein® Fibre® has proved a formula for enteral nutrition well tolerated, with a very low frequency of gastrointestinal symptoms and an improvement in the number of stools, which encourages compliance with the standard prescribed by the health professional and suggest a positive effect on the regulation of intestinal transit. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

I(f) current inhibitor ivabradine in patients with idiopathic dilated cardiomyopathy: Impact on the exercise tolerance and quality of life.

PubMed

Abdel-Salam, Zainab; Rayan, Mona; Saleh, Ayman; Abdel-Barr, Mohamed G; Hussain, Mohamed; Nammas, Wail

2015-01-01

Evidence supported a beneficial effect of ivabradine on clinical outcome of patients with systolic heart failure, and a sinus heart rate (HR) ≥ 70 bpm. We explored the effect of ivabradine, vs. placebo, added to evidence-based treatment on exercise tolerance and quality of life in patients with idiopathic dilated cardiomyopathy. We enrolled 43 consecutive patients with dilated cardiomyopathy of no apparent cause, a left ventricular ejection fraction (LVEF) < 40%, New York Heart Association class ≥ II, sinus HR ≥ 70 bpm, and background evidence-based anti-failure medications. Ischemic heart disease was ruled out. Patients were randomized (1:1) to receive ivabradine or placebo. Ivabradine was titrated up gradually till 7.5 mg twice daily, or a HR < 60 bpm, and continued for 3 months. Symptom-limited exercise tolerance test was performed, and quality of life was assessed by the Minnesota Living With Heart Failure Questionnaire at 0, and 3 months. Forty-three patients were randomized to ivabradine (n = 20), or placebo (n = 23). Mean age was 50.8 ± 14.5 years (53.5% males). Mean HR was 85 ± 12 bpm, and mean LVEF was 32 ± 6%. Mean dose of carvedilol was 31.2% of the target dose. Baseline HR, blood pressure, exercise tolerance, Minnesota questionnaire score, and left ventricular systolic function were comparable between the two groups (p > 0.05 for all). At 3 months, mean dose of ivabradine was 6.8 mg bid. Ivabradine-treated patients had a lower HR, and improved left ventricular dimensions and systolic function, versus placebo-treated ones (p < 0.05 for all). HR dropped by a mean of 14 bpm in the ivabradine group, corrected for placebo. Both exercise tolerance, and Minnesota questionnaire score were better in the ivabradine group (p < 0.05 both). Ivabradine was well-tolerated. In symptomatic patients with idiopathic dilated cardiomyopathy, the addition of ivabradine, vs. placebo, to evidence-based treatment, reduced HR, and improved functional capacity, at short-term follow-up.

Over-expression of the Pseudomonas syringae harpin-encoding gene hrpZm confers enhanced tolerance to Phytophthora root and stem rot in transgenic soybean.

PubMed

Du, Qian; Yang, Xiangdong; Zhang, Jinhua; Zhong, Xiaofang; Kim, Kyung Seok; Yang, Jing; Xing, Guojie; Li, Xiaoyu; Jiang, Zhaoyuan; Li, Qiyun; Dong, Yingshan; Pan, Hongyu

2018-06-01

Phytophthora root and stem rot (PRR) caused by Phytophthora sojae is one of the most devastating diseases reducing soybean (Glycine max) production all over the world. Harpin proteins in many plant pathogenic bacteria were confirmed to enhance disease and insect resistance in crop plants. Here, a harpin protein-encoding gene hrpZpsta from the P. syringae pv. tabaci strain Psta218 was codon-optimized (renamed hrpZm) and introduced into soybean cultivars Williams 82 and Shennong 9 by Agrobacterium-mediated transformation. Three independent transgenic lines over-expressing hrpZm were obtained and exhibited stable and enhanced tolerance to P. sojae infection in T 2 -T 4 generations compared to the non-transformed (NT) and empty vector (EV)-transformed plants. Quantitative real-time PCR (qRT-PCR) analysis revealed that the expression of salicylic acid-dependent genes PR1, PR12, and PAL, jasmonic acid-dependent gene PPO, and hypersensitive response (HR)-related genes GmNPR1 and RAR was significantly up-regulated after P. sojae inoculation. Moreover, the activities of defense-related enzymes such as phenylalanine ammonia lyase (PAL), polyphenoloxidase (PPO), peroxidase, and superoxide dismutase also increased significantly in the transgenic lines compared to the NT and EV-transformed plants after inoculation. Our results suggest that over-expression of the hrpZm gene significantly enhances PRR tolerance in soybean by eliciting resistance responses mediated by multiple defense signaling pathways, thus providing an alternative approach for development of soybean varieties with improved tolerance against the soil-borne pathogen PRR.

A Randomized, Placebo-Controlled Trial of Latrepirdine in Huntington Disease

PubMed Central

Kieburtz, Karl; McDermott, Michael P.; Voss, Tiffini S.; Corey-Bloom, Jody; Deuel, Lisa M.; Dorsey, E. Ray; Factor, Stewart; Geschwind, Michael D.; Hodgeman, Karen; Kayson, Elise; Noonberg, Sarah; Pourfar, Michael; Rabinowitz, Karen; Ravina, Bernard; Sanchez-Ramos, Juan; Seely, Lynn; Walker, Francis; Feigin, Andrew

2014-01-01

Objectives To evaluate the safety and tolerability of latrepirdine in Huntington disease (HD) and explore its effects on cognition, behavior, and motor symptoms. Design Double-blind, randomized, placebo-controlled trial. Setting Multicenter outpatient trial. Participants Ninety-one participants with mild to moderate HD enrolled at 17 US and UK centers from July 18, 2007, through July 16, 2008. Intervention Latrepirdine, 20 mg 3 times daily (n=46), or matching placebo (n=45) for a 90-day treatment period. Main Outcome Measures The primary outcome variable was tolerability, defined as the ability to complete the study at the assigned drug dosage. Secondary outcome variables included score changes from baseline to day 90 on the Unified Huntington's Disease Rating Scale (UHDRS), the Mini-Mental State Examination (MMSE), and the Alzheimer Disease Assessment Scale–cognitive subscale (ADAS-cog). Results Latrepirdine was well tolerated (87% of the patients given latrepirdine completed the study vs 82% in the placebo group), and adverse event rates were comparable in the 2 groups (70% in the latrepirdine group and 80% in the placebo group). Treatment with latrepirdine resulted in improved mean MMSE scores compared with stable performance in the placebo group (treatment effect, 0.97 points; 95% confidence interval, 0.10-1.85; P=.03). No significant treatment effects were seen on the UHDRS or the ADAS-cog. Conclusions Short-term administration of latrepirdine is well tolerated in patients with HD and may have a beneficial effect on cognition. Further investigation of latrepirdine is warranted in this population with HD. PMID:20142523

Comparative transcriptome profiling of potassium starvation responsiveness in two contrasting watermelon genotypes.

PubMed

Fan, Molin; Huang, Yuan; Zhong, Yaqin; Kong, Qiusheng; Xie, Junjun; Niu, Mengliang; Xu, Yong; Bie, Zhilong

2014-02-01

Potassium (K) is one of the essential nutrients for crops, and K⁺ deficiency highly restricts crop yield and quality. Watermelon [Citrullus lanatus (Thunb.) Matsum. & Nakai] is an economically important crop that often suffers from K⁺ deficiency. To elucidate the underlying tolerance mechanism of watermelon to K⁺ deficiency and to improve K efficiency of watermelon and other crops in the future, two watermelon genotypes, namely, YS and 8424, that exhibit contrasting K efficiencies were studied to compare their response mechanisms to K⁺ deficiency. YS was more tolerant of K⁺ deficiency and displayed less inhibited root growth than 8424. Roots of YS and 8424 seedlings with or without K⁺ supply were harvested at 6 and 120 h after treatment (HAT), and their transcriptomes were analyzed by Illumina RNA sequencing. Different regulation mechanisms of the root K⁺-uptake genes for short- and long-term stress were observed. Genes involved in jasmonic acid and reactive oxygen species production; Ca²⁺ and receptor-like kinase signaling; lignin biosynthesis; and other stress-related genes were repressed in YS, whereas a large number of such stress-related genes were induced in 8424 at 120 HAT. These results suggested that repressed defense and stress response can save energy for better root growth in YS, which can facilitate K⁺ uptake and increase K efficiency and tolerance to K⁺ deficiency. This study presents the first global root transcriptome in watermelon and provides new insights into the molecular mechanisms underlying tolerance to K⁺ deficiency of K-efficient watermelon genotypes.

Testosterone is protective against impaired glucose metabolism in male intrauterine growth-restricted offspring

PubMed Central

Dasinger, John Henry; Fahling, Joel M.; Backstrom, Miles A.; Alexander, Barbara T.

2017-01-01

Placental insufficiency alters the intrauterine environment leading to increased risk for chronic disease including impaired glucose metabolism in low birth weight infants. Using a rat model of low birth weight, we previously reported that placental insufficiency induces a significant increase in circulating testosterone in male intrauterine growth-restricted offspring (mIUGR) in early adulthood that is lost by 12 months of age. Numerous studies indicate testosterone has a positive effect on glucose metabolism in men. Female growth-restricted littermates exhibit glucose intolerance at 6 months of age. Thus, the aim of this paper was to determine whether mIUGR develop impaired glucose metabolism, and whether a decrease in elevated testosterone levels plays a role in its onset. Male growth-restricted offspring were studied at 6 and 12 months of age. No impairment in glucose tolerance was observed at 6 months of age when mIUGR exhibited a 2-fold higher testosterone level compared to age-matched control. Fasting blood glucose was significantly higher and glucose tolerance was impaired with a significant decrease in circulating testosterone in mIUGR at 12 compared with 6 months of age. Castration did not additionally impair fasting blood glucose or glucose tolerance in mIUGR at 12 months of age, but fasting blood glucose was significantly elevated in castrated controls. Restoration of elevated testosterone levels significantly reduced fasting blood glucose and improved glucose tolerance in mIUGR. Thus, our findings suggest that the endogenous increase in circulating testosterone in mIUGR is protective against impaired glucose homeostasis. PMID:29145418

Single-dose lubiprostone along with split-dose PEG solution without dietary restrictions for bowel cleansing prior to colonoscopy: a randomized, double-blind, placebo-controlled trial.

PubMed

Stengel, Joel Z; Jones, David P

2008-09-01

Proper colonic cleansing prior to colonoscopy is paramount to ensuring complete mucosal visualization and polyp identification. In a double-blind fashion, we compared single-dose lubiprostone (24 microg) versus placebo pretreatment prior to a split-dose polyethylene glycol electrolyte (PEG-E) bowel preparation without dietary restriction to determine the efficacy, safety, and patient tolerability. Two hundred patients referred for outpatient colorectal cancer screening were randomized to receive a single-dose of unlabeled lubiprostone (24 microg) or placebo prior to a split-dose PEG-E bowel preparation without dietary restriction. The patients were surveyed prior to the colonoscopy on the tolerability of the bowel preparation, and any adverse events were recorded. The cleanliness of the colon was graded by the endoscopist during the procedure utilizing the Ottawa bowel preparation scale. One hundred ninety-one patients completed the study (95%). Split-dose PEG-E with lubiprostone pretreatment was found to be more effective at bowel cleansing in each segment of the colon when compared with split-dose PEG-E with placebo (P < 0.001). Patients enrolled in the lubiprostone treatment arm rated the overall experience as more tolerable (P 0.003) and complained of less abdominal bloating (P 0.049). No differences were observed between the groups for treatment-emergent side effects or adverse events (P > 0.05). Single-dose lubiprostone prior to split-dose PEG-E without dietary restriction significantly improves colonic mucosa visualization during colonoscopy and is well tolerated by patients.

The value of oxybutynin in transdermal patches for treating overactive bladder.

PubMed

Salinas-Casado, J; Esteban-Fuertes, M; Serrano, O; Galván, J

2015-12-01

There is currently a broad therapeutic arsenal of drugs for treating overactive bladder syndrome (OAB). However, there is still a need for new compounds and for improving known drugs in terms of efficacy, compliance and tolerability. To report the scientific evidence on the safety and efficacy of transdermal oxybutynin (OXY-TDS) for treating OAB. A systematic review without time restrictions was conducted until May 2015 in the MEDLINE/PubMed database. We also performed a manual review of abstracts published in international urogynaecology congresses. The evaluated studies show that patients treated with OXY-TDS experience a significant reduction in urinary incontinence episodes compared with placebo, which is comparable to that observed in patients treated with oral oxybutynin or with tolterodine. In all of the studies, we observed improvements in symptoms from the second or third week of treatment and in a sustained manner until the end of treatment (6, 12 or 24 weeks). The clinical practice study also showed improved quality of life, achieving benefits in numerous patient profiles, with an efficacy independent of previous treatments. The safety of the drug was demonstrated in the various patient profiles. OXY-TDS represents an effective alternative for the symptomatic treatment of adult patients with OAB, which, thanks to its pharmacokinetic profile, better tolerability, different administration method and dosage, could represent an added value in treating special populations. Copyright © 2015 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Expression of Arabidopsis glycine-rich RNA-binding protein AtGRP2 or AtGRP7 improves grain yield of rice (Oryza sativa) under drought stress conditions.

PubMed

Yang, Deok Hee; Kwak, Kyung Jin; Kim, Min Kyung; Park, Su Jung; Yang, Kwang-Yeol; Kang, Hunseung

2014-01-01

Although posttranscriptional regulation of RNA metabolism is increasingly recognized as a key regulatory process in plant response to environmental stresses, reports demonstrating the importance of RNA metabolism control in crop improvement under adverse environmental stresses are severely limited. To investigate the potential use of RNA-binding proteins (RBPs) in developing stress-tolerant transgenic crops, we generated transgenic rice plants (Oryza sativa) that express Arabidopsis thaliana glycine-rich RBP (AtGRP) 2 or 7, which have been determined to harbor RNA chaperone activity and confer stress tolerance in Arabidopsis, and analyzed the response of the transgenic rice plants to abiotic stresses. AtGRP2- or AtGRP7-expressing transgenic rice plants displayed similar phenotypes comparable with the wild-type plants under high salt or cold stress conditions. By contrast, AtGRP2- or AtGRP7-expressing transgenic rice plants showed much higher recovery rates and grain yields compared with the wild-type plants under drought stress conditions. The higher grain yield of the transgenic rice plants was due to the increases in filled grain numbers per panicle. Collectively, the present results show the importance of posttranscriptional regulation of RNA metabolism in plant response to environmental stress and suggest that GRPs can be utilized to improve the yield potential of crops under stress conditions. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Heterologous expression of a plastid EF-Tu reduces protein thermal aggregation and enhances CO2 fixation in wheat (Triticum aestivum) following heat stress.

PubMed

Fu, Jianming; Momcilović, Ivana; Clemente, Thomas E; Nersesian, Natalya; Trick, Harold N; Ristic, Zoran

2008-10-01

Heat stress is a major constraint to wheat production and negatively impacts grain quality, causing tremendous economic losses, and may become a more troublesome factor due to global warming. At the cellular level, heat stress causes denaturation and aggregation of proteins and injury to membranes leading to alterations in metabolic fluxes. Protein aggregation is irreversible, and protection of proteins from thermal aggregation is a strategy a cell uses to tolerate heat stress. Here we report on the development of transgenic wheat (Triticum aestivum) events, expressing a maize gene coding for plastidal protein synthesis elongation factor (EF-Tu), which, compared to non-transgenic plants, display reduced thermal aggregation of leaf proteins, reduced heat injury to photosynthetic membranes (thylakoids), and enhanced rate of CO(2) fixation after exposure to heat stress. The results support the concept that EF-Tu ameliorates negative effects of heat stress by acting as a molecular chaperone. This is the first demonstration of the introduction of a plastidal EF-Tu in plants that leads to protection against heat injury and enhanced photosynthesis after heat stress. This is also the first demonstration that a gene other than HSP gene can be used for improvement of heat tolerance and that the improvement is possible in a species that has a complex genome, hexaploid wheat. The results strongly suggest that heat tolerance of wheat, and possibly other crop plants, can be improved by modulating expression of plastidal EF-Tu and/or by selection of genotypes with increased endogenous levels of this protein.

Freezing and desiccation tolerance in entomopathogenic nematodes: diversity and correlation of traits.

PubMed

Shapiro-Ilan, David I; Brown, Ian; Lewis, Edwin E

2014-03-01

The ability of entomopathogenic nematodes to tolerate environmental stress such as desiccating or freezing conditions, can contribute significantly to biocontrol efficacy. Thus, in selecting which nematode to use in a particular biocontrol program, it is important to be able to predict which strain or species to use in target areas where environmental stress is expected. Our objectives were to (i) compare inter- and intraspecific variation in freeze and desiccation tolerance among a broad array of entomopathogenic nematodes, and (ii) determine if freeze and desiccation tolerance are correlated. In laboratory studies we compared nematodes at two levels of relative humidity (RH) (97% and 85%) and exposure periods (24 and 48 h), and nematodes were exposed to freezing temperatures (-2°C) for 6 or 24 h. To assess interspecific variation, we compared ten species including seven that are of current or recent commercial interest: Heterorhabditis bacteriophora (VS), H. floridensis, H. georgiana, (Kesha), H. indica (HOM1), H. megidis (UK211), Steinernema carpocapsae (All), S. feltiae (SN), S. glaseri (VS), S. rarum (17C&E), and S. riobrave (355). To assess intraspecific variation we compared five strains of H. bacteriophora (Baine, Fl1-1, Hb, Oswego, and VS) and four strains of S. carpocapsae (All, Cxrd, DD136, and Sal), and S. riobrave (355, 38b, 7-12, and TP). S. carpocapsae exhibited the highest level of desiccation tolerance among species followed by S. feltiae and S. rarum; the heterorhabditid species exhibited the least desiccation tolerance and S. riobrave and S. glaseri were intermediate. No intraspecific variation was observed in desiccation tolerance; S. carpocapsae strains showed higher tolerance than all H. bacteriophora or S. riobrave strains yet there was no difference detected within species. In interspecies comparisons, poor freeze tolerance was observed in H. indica, and S. glaseri, S. rarum, and S. riobrave whereas H. georgiana and S. feltiae exhibited the highest freeze tolerance, particularly in the 24-h exposure period. Unlike desiccation tolerance, substantial intraspecies variation in freeze tolerance was observed among H. bacteriophora and S. riobrave strains, yet within species variation was not detected among S. carpocapsae strains. Correlation analysis did not detect a relationship between freezing and desiccation tolerance.

Improving microbial biogasoline production in Escherichia coli using tolerance engineering.

PubMed

Foo, Jee Loon; Jensen, Heather M; Dahl, Robert H; George, Kevin; Keasling, Jay D; Lee, Taek Soon; Leong, Susanna; Mukhopadhyay, Aindrila

2014-11-04

Engineering microbial hosts for the production of fungible fuels requires mitigation of limitations posed on the production capacity. One such limitation arises from the inherent toxicity of solvent-like biofuel compounds to production strains, such as Escherichia coli. Here we show the importance of host engineering for the production of short-chain alcohols by studying the overexpression of genes upregulated in response to exogenous isopentenol. Using systems biology data, we selected 40 genes that were upregulated following isopentenol exposure and subsequently overexpressed them in E. coli. Overexpression of several of these candidates improved tolerance to exogenously added isopentenol. Genes conferring isopentenol tolerance phenotypes belonged to diverse functional groups, such as oxidative stress response (soxS, fpr, and nrdH), general stress response (metR, yqhD, and gidB), heat shock-related response (ibpA), and transport (mdlB). To determine if these genes could also improve isopentenol production, we coexpressed the tolerance-enhancing genes individually with an isopentenol production pathway. Our data show that expression of 6 of the 8 candidates improved the production of isopentenol in E. coli, with the methionine biosynthesis regulator MetR improving the titer for isopentenol production by 55%. Additionally, expression of MdlB, an ABC transporter, facilitated a 12% improvement in isopentenol production. To our knowledge, MdlB is the first example of a transporter that can be used to improve production of a short-chain alcohol and provides a valuable new avenue for host engineering in biogasoline production. The use of microbial host platforms for the production of bulk commodities, such as chemicals and fuels, is now a focus of many biotechnology efforts. Many of these compounds are inherently toxic to the host microbe, which in turn places a limit on production despite efforts to optimize the bioconversion pathways. In order to achieve economically viable production levels, it is also necessary to engineer production strains with improved tolerance to these compounds. We demonstrate that microbial tolerance engineering using transcriptomics data can also identify targets that improve production. Our results include an exporter and a methionine biosynthesis regulator that improve isopentenol production, providing a starting point to further engineer the host for biogasoline production. Copyright © 2014 Foo et al.

Oral N-acetylcysteine and exercise tolerance in mild chronic obstructive pulmonary disease.

PubMed

Hirai, Daniel M; Jones, Joshua H; Zelt, Joel T; da Silva, Marianne L; Bentley, Robert F; Edgett, Brittany A; Gurd, Brendon J; Tschakovsky, Michael E; O'Donnell, Denis E; Neder, J Alberto

2017-05-01

Heightened oxidative stress is implicated in the progressive impairment of skeletal muscle vascular and mitochondrial function in chronic obstructive pulmonary disease (COPD). Whether accumulation of reactive oxygen species contributes to exercise intolerance in the early stages of COPD is unknown. The purpose of the present study was to determine the effects of oral antioxidant treatment with N -acetylcysteine (NAC) on respiratory, cardiovascular, and locomotor muscle function and exercise tolerance in patients with mild COPD. Thirteen patients [forced expiratory volume in 1 s (FEV 1 )-to-forced vital capacity ratio < lower limit of normal (LLN) and FEV 1 ≥ LLN) were enrolled in a double-blind, randomized crossover study to receive NAC (1,800 mg/day) or placebo for 4 days. Severe-intensity constant-load exercise tests were performed with noninvasive measurements of central hemodynamics (stroke volume, heart rate, and cardiac output via impedance cardiography), arterial blood pressure, pulmonary ventilation and gas exchange, quadriceps muscle oxygenation (near-infrared spectroscopy), and estimated capillary blood flow. Nine patients completed the study with no major adverse clinical effects. Although NAC elevated plasma glutathione by ~27% compared with placebo ( P < 0.05), there were no differences in exercise tolerance (placebo: 325 ± 47 s, NAC: 336 ± 51 s), central hemodynamics, arterial blood pressure, pulmonary ventilation or gas exchange, locomotor muscle oxygenation, or capillary blood flow from rest to exercise between conditions ( P > 0.05 for all). In conclusion, modulation of plasma redox status with oral NAC treatment was not translated into beneficial effects on central or peripheral components of the oxygen transport pathway, thereby failing to improve exercise tolerance in nonhypoxemic patients with mild COPD. NEW & NOTEWORTHY Acute antioxidant treatment with N -acetylcysteine (NAC) elevated plasma glutathione but did not modulate central or peripheral components of the O 2 transport pathway, thereby failing to improve exercise tolerance in patients with mild chronic obstructive pulmonary disease (COPD). Copyright © 2017 the American Physiological Society.

Exposure to lower red to far-red light ratios improve tomato tolerance to salt stress.

PubMed

Cao, Kai; Yu, Jie; Xu, Dawei; Ai, Kaiqi; Bao, Encai; Zou, Zhirong

2018-05-24

Red (R) and far-red (FR) light distinctly influence phytochrome-mediated initial tomato growth and development, and more recent evidence indicates that these spectra also modulate responses to a multitude of abiotic and biotic stresses. This research investigated whether different R: FR values affect tomato growth response and salinity tolerance. Tomato seedlings were exposed to different R: FR conditions (7.4, 1.2 and 0.8) under salinity stress (100 mM NaCl), and evaluated for their growth, biochemical changes, active reactive oxygen species (ROS) and ROS scavenging enzymes, pigments, rate of photosynthesis, and chlorophyll fluorescence. The results showed that under conditions of salinity, tomato seedlings subjected to a lower R: FR value (0.8) significantly increased both their growth, proline content, chlorophyll content and net photosynthesis rate (Pn), while they decreased malondialdehyde (MDA) compared to the higher R: FR value (7.4). Under conditions of salinity, the lower R: FR value caused a decrease in both the superoxide anion (O 2 •- ) and in hydrogen peroxide (H 2 O 2 ) generation, an increase in the activities of superoxidase dismutase (SOD, EC 1.15.1.1), peroxidase (POD, EC 1.11.1.7) and catalase (CAT, EC 1.11.1.7). Tomato seedlings grown under the lower R: FR value and conditions of salinity showed a higher actual quantum yield of photosynthesis (ΦPSII), electron transport rate (ETR), and photochemical quenching (qP) than those exposed to a higher R: FR, indicating overall healthier growth. However, the salinity tolerance induced at the lower R: FR condition disappeared in the tomato phyB1 mutant. These results suggest that growing tomato with a lower R: FR value could improve seedlings' salinity tolerance, and phytochrome B1 play an very important role in this process. Therefore, different qualities of light can be used to efficiently develop abiotic stress tolerance in tomato cultivation.

Tolerance limits and methodologies for IMRT measurement-based verification QA: Recommendations of AAPM Task Group No. 218.

PubMed

Miften, Moyed; Olch, Arthur; Mihailidis, Dimitris; Moran, Jean; Pawlicki, Todd; Molineu, Andrea; Li, Harold; Wijesooriya, Krishni; Shi, Jie; Xia, Ping; Papanikolaou, Nikos; Low, Daniel A

2018-04-01

Patient-specific IMRT QA measurements are important components of processes designed to identify discrepancies between calculated and delivered radiation doses. Discrepancy tolerance limits are neither well defined nor consistently applied across centers. The AAPM TG-218 report provides a comprehensive review aimed at improving the understanding and consistency of these processes as well as recommendations for methodologies and tolerance limits in patient-specific IMRT QA. The performance of the dose difference/distance-to-agreement (DTA) and γ dose distribution comparison metrics are investigated. Measurement methods are reviewed and followed by a discussion of the pros and cons of each. Methodologies for absolute dose verification are discussed and new IMRT QA verification tools are presented. Literature on the expected or achievable agreement between measurements and calculations for different types of planning and delivery systems are reviewed and analyzed. Tests of vendor implementations of the γ verification algorithm employing benchmark cases are presented. Operational shortcomings that can reduce the γ tool accuracy and subsequent effectiveness for IMRT QA are described. Practical considerations including spatial resolution, normalization, dose threshold, and data interpretation are discussed. Published data on IMRT QA and the clinical experience of the group members are used to develop guidelines and recommendations on tolerance and action limits for IMRT QA. Steps to check failed IMRT QA plans are outlined. Recommendations on delivery methods, data interpretation, dose normalization, the use of γ analysis routines and choice of tolerance limits for IMRT QA are made with focus on detecting differences between calculated and measured doses via the use of robust analysis methods and an in-depth understanding of IMRT verification metrics. The recommendations are intended to improve the IMRT QA process and establish consistent, and comparable IMRT QA criteria among institutions. © 2018 American Association of Physicists in Medicine.

Different effect of handle region peptide on β-cell function in different sexes of rats neonatally treated with sodium L-glutamate.

PubMed

Wu, Yi-xi; Sun, Ru-qiong; Yin, Guo-shu; Xu, Dong-chuan; Wang, Ping; Lin, Kun; Lin, Chu-jia; Lin, Shao-da

2015-03-17

BACKGROUND The (pro)renin receptor ((P)RR) was reported to be expressed in various tissues including the pancreas, and handle region peptide (HRP) is believed to block the function of (P)RR. This study aimed to investigate the effect of HRP on the glucose tolerance status and β-cell function of female rats, neonatally treated with sodium L-glutamate (MSG) and to compare with the previously reported HRP effect on male rats. MATERIAL AND METHODS Female MSG rats aged 8 weeks were divided into MSG control group and HRP treated group and the normal SD rats served as control. The MSG rats were treated with HRP by osmotic minipumps with dose of 1 mg/kg per day for total 28 days. Glucose tolerance status was evaluated at the end of the study. Islets α-cell and β-cell were marked with insulin antibody and glucagon antibody respectively. The proliferation of islet cells and expression of subunit of NADPH oxidase P22phox were marked by PCNA and P22phox antibody. Picrosirius red staining was performed for evaluating fibrosis of islets. RESULTS HRP improved the glucose status tolerance with decreasing α-cell mass, islets PCNA-positive cells, expression of P22phox and picrosirius red stained areas, and increasing β-cell mass in female MSG rats. The indexes with obviously interacted effect of sexes and HRP for the MSG rats were the AUC of blood glucose concentration (P<0.01), α-cell mass (P<0.05), proliferation of islet cells (P<0.01) and area of picrosirius red staining (P<0.01). CONCLUSIONS HRP improved the glucose tolerance status in the females although it was previously reported to worsen the glucose tolerance in male MSG rats. Different levels of sex hormones may partly account for the disparate effects observed for HRP in different sexes.

Different Effect of Handle Region Peptide on β-Cell Function in Different Sexes of Rats Neonatally Treated with Sodium L-Glutamate

PubMed Central

Wu, Yi-xi; Sun, Ru-qiong; Yin, Guo-shu; Xu, Dong-chuan; Wang, Ping; Lin, Kun; Lin, Chu-jia; Lin, Shao-da

2015-01-01

Background The (pro)renin receptor ((P)RR) was reported to be expressed in various tissues including the pancreas, and handle region peptide (HRP) is believed to block the function of (P)RR. This study aimed to investigate the effect of HRP on the glucose tolerance status and β-cell function of female rats, neonatally treated with sodium L-glutamate (MSG) and to compare with the previously reported HRP effect on male rats. Material/Methods Female MSG rats aged 8 weeks were divided into MSG control group and HRP treated group and the normal SD rats served as control. The MSG rats were treated with HRP by osmotic minipumps with dose of 1 mg/kg per day for total 28 days. Glucose tolerance status was evaluated at the end of the study. Islets α-cell and β-cell were marked with insulin antibody and glucagon antibody respectively. The proliferation of islet cells and expression of subunit of NADPH oxidase P22phox were marked by PCNA and P22phox antibody. Picrosirius red staining was performed for evaluating fibrosis of islets. Results HRP improved the glucose status tolerance with decreasing α-cell mass, islets PCNA-positive cells, expression of P22phox and picrosirius red stained areas, and increasing β-cell mass in female MSG rats. The indexes with obviously interacted effect of sexes and HRP for the MSG rats were the AUC of blood glucose concentration (P<0.01), α-cell mass (P<0.05), proliferation of islet cells (P<0.01) and area of picrosirius red staining (P<0.01). Conclusions HRP improved the glucose tolerance status in the females although it was previously reported to worsen the glucose tolerance in male MSG rats. Different levels of sex hormones may partly account for the disparate effects observed for HRP in different sexes. PMID:25783768